index
stringlengths 10
17
| text
stringlengths 101
18k
| doi
stringlengths 2
72
|
|---|---|---|
pubmed_143_7862 | Parkinson's disease (PD) is a progressive neurodegenerative disease, with a worldwide incidence of 1% in individuals >60 years of age. Its primary characteristics include postural impairments and changes in circadian rhythms. The authors investigated the association between postural impairment and changes in circadian rhythms in 24 PD subjects diagnosed with stages 1 to 3 on the Hoehn-Yard (HY) scale and regularly used dopaminergic medication for at least 1 year (experimental group - EG) and 24 healthy elderly individuals without a history of neurological impairment as the control group (CG). Static balance tests using a force plate were performed, and activity/rest rhythm, according to the relative amplitude of L5 and M10 values, was monitored for seven consecutive days using actimetry. The results indicated differences in posturographic indicators of mediolateral displacement (ML) [EG, 4.71 ± 0.85 mm; CG, 2.79 ± 0.53 mm (p < .0001)] and anteroposterior displacement of the center of pressure (COP) [EG, 5.61 ± 2.43 mm; CG, 8.23 ± 1.72 mm (< 0.0001)], ML velocity of the COP [EG, 2.39 ± 0.83 mm/s; CG, 1.40 ± 0.18 mm/s (p < .0001)], and total distance of the COP in the tandem stance condition [EG, 227.6 ± 75 mm; CG, 53.4 ± 6.1 mm (p < .0001)] between the EG and CG. There was no correlation between relative amplitude and posturographic data for the EG. Postural impairments were verified in comparing the EG and CG; however, there was no association between posturographic indicators and activity/rest rhythm. | 10.1080/07420528.2019.1692350 |
pubmed_224_5613 | A mitochondrial preparation from adult duck adrenal gland was used to study the mechanism (dehydrogenation or other) of the last step of aldosterone biosynthesis (18-oxidation) by incubation of tritiated 18-hydroxycorticosterone. Results show that the role of citric acid cycle metabolites is to provide reducing power. When reducing power is provided by malate, which yields NADH or NADPH directly, the reoxidation of reduced coenzymes in the oxidative phosphorylation chain is not necessary. In the presence of succinate, the oxidative phosphorylation chain is required, but only to provide ATP. Stimulation of the reaction by low concentrations of KCN in the presence of malate shows that the reducing power is not used in the oxidative phosphorylation chain. These data suggest that the reaction is not a dehydrogenation and that the reducing power is used in a pathway competing with the respiratory chain, most probably a hydroxylating pathway, in mitochondria. | 10.1016/0005-2760(83)90234-5 |
pubmed_301_11280 | A 12-year-old male cat with depression and dyspnoea was presented for investigation. Radiography and computed tomography revealed hydrothorax and solid masses involving the sternum, ribs and thoracic vertebrae. The cat died two days after first presentation, and postmortem examination revealed lung masses and proliferative bony lesions. Histologically, a neoplastic proliferation of epithelial cells was seen in the lungs, with a large amount of collagen and deposits of cholesterin. The bone lesions were also composed of neoplastic epithelial cells and abundant calcified osteoid, without atypia. A diagnosis of pulmonary adenocarcinoma with osteoblastic bone metastases was made. This is the first reported case of osteoblastic metastases in the cat. | 10.1111/j.1748-5827.2003.tb00107.x |
pubmed_1034_11142 | Polyphenols, ascorbic acid content and antioxidant activity of two sweet oranges (Navel-N and Cara Cara-CC) and mandarin (Clementine-M) as well as their bioaccessibilities were evaluated in pulps and compared to those in fresh juice. Thus, pulps of oranges and mandarins displayed higher hesperidin (HES), narirutin (NAR), total flavonoids (TF), total phenols (TP) and antioxidant activity (AAC) than their corresponding juices. Also, CC products presented higher bioactive compounds content than N ones. Bioaccessibility of bioactive compounds and AAC were higher in pulps of both oranges and mandarin than in their corresponding juices. Oranges (N and CC) pulps and juices presented higher bioaccessibilities than mandarin ones. The postharvest storage of mandarin at 12°C during 5weeks not only produced a significant increase of the bioactive compounds but also an increase of their bioaccessibility. The bioaccessibility of Citrus bioactive compounds is necessary for calculating more accurately their daily intake amount. | 10.1016/j.foodchem.2016.12.098 |
pubmed_968_7279 | OBJECTIVE
This study investigated the occurrence of postictal agitation (PA) in patients undergoing an acute series of electroconvulsive therapy (ECT) and further explored patient and treatment variables associated with PA.
METHODS
Charts were retrospectively searched for patients undergoing an acute series of ECT. Postictal agitation was identified by the administration of a sedative after ECT. Demographic, diagnostic, medication, and ECT variables that could also be associated with PA were collected and accounted for in statistical analysis.
RESULTS
In this population, 22 of 156 patients experienced PA. Associations that reached statistical significance included sex, weight, active substance use disorder, seizure duration (as observed by motor movements), and waking time. Only seizure duration and waking time maintained significance after multivariable analysis.
CONCLUSIONS
These data identify clinical factors that could help predict PA. Patients with greater weight, male sex, or an active substance use disorder ought to be carefully monitored for PA, and staff in the recovery suite should be especially vigilant about such patients with longer seizures and waking times. | 10.1097/YCT.0000000000000807 |
pubmed_716_20160 | Exosomes, a subset of extracellular vesicles, are widely present in various body fluids and are involved in mediating intercellular communication. They have received extensive attention as diagnostic markers. The excellent physicochemical and biological properties of exosomes make them great potential drug delivery vehicles for the treatment of cancer and other diseases. However, various challenges need to be addressed for the clinical application of exosomes. This review introduces the biogenesis and uptake of exosomes and compares different approaches for isolation and drug loading, focusing on the application and current challenges of exosomes as drug delivery vehicles in cancer therapy. | 10.31083/j.fbl2710293 |
pubmed_616_16180 | PURPOSE
Advances in surgical techniques allow implantation of intraocular lenses (IOL) with cataract extraction, even in young children. However, there are several challenges unique to the pediatric population that result in greater degrees of postoperative refractive error compared to adults.
METHODS
Literature review of the techniques and outcomes of pediatric cataract surgery with IOL implantation.
RESULTS
Pediatric cataract surgery is associated with several sources of postoperative refractive error. These include planned refractive error based on age or fellow eye status, loss of accommodation, and unexpected refractive errors due to inaccuracies in biometry technique, use of IOL power formulas based on adult normative values, and late refractive changes due to unpredictable eye growth.
CONCLUSIONS
Several factors can preclude the achievement of optimal refractive status following pediatric cataract extraction with IOL implantation. There is a need for new technology to reduce postoperative refractive surprises and address refractive adjustment in a growing eye. | 10.1080/08820538.2017.1353812 |
pubmed_1064_18561 | BACKGROUND
Patients with osteoarthritis of the knee can be treated with a brace or orthosis (shoe insole). The main purpose of these aids is to reduce pain, improve physical function and, possibly, to slow disease progression.
OBJECTIVES
To assess the effectiveness of a brace or orthosis in the treatment of osteoarthritis of the knee.
SEARCH STRATEGY
We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE (Current contents, Health STAR) up to October 2002. The reference lists of the publications in the identified trials were also screened.
SELECTION CRITERIA
Extracted studies were included in the final analysis if they met the pre-defined inclusion criteria: 1) a randomised controlled clinical trial or a controlled clinical trial, 2) all patients had osteoarthritis of the knee, 3) the intervention in one of the studied groups was a brace or an orthosis.
DATA COLLECTION AND ANALYSIS
Two reviewers independently selected the trials and assessed the methodological quality using the Delphi-list and one additional question about care programs. Three reviewers independently extracted the data on the intervention, type of outcome measures, follow-up, loss to follow-up, and results, using a pre-tested standardized form. Study authors were contacted for additional information.
MAIN RESULTS
Four trials involving a total of 444 people were included in this review. One study investigated a knee brace and three studies examined different types of orthoses for medial compartment osteoarthritis of the knee. Two studies were of high methodological quality while the other two studies were low. Notably, the randomisation and the blinding procedures were either insufficient or not described. The follow-up period (six weeks to six months) was too short to demonstrate long-term results. Pooling was difficult primarily due to the heterogeneity of the data and the way the information was presented. The pain, stiffness and physical function (WOMAC and MACTAR) scores of a brace group showed greater improvement at six months compared with a neoprene sleeve group, which showed greater improvement compared with a control group. The numbers of days of non-steroidal anti-inflammatory drug (NSAID) intake decreased significantly (relative percentage difference 23.9%) compared with baseline in a group with laterally wedged insoles,and remained unchanged in the neutrally wedged group. Patient compliance with the laterally wedged insole was significantly better compared with the neutrally wedged insole. In one study, the Visual Analogue Pain (VAS) pain score was significantly decreased from baseline in a strapped insole group (RPD - 24%), but not in the traditional lateral wedge group, but this strapped insole showed more adverse effects (popliteal pain, low back pain, and foot sole pain) compared with the traditional lateral wedge insole. Pain during bed rest, after getting up, after getting up from seated position and walking distance was significantly improved in a subtalar strapped group compared with baseline, and no improvement was found in a sock type group. No studies were found that assessed the effectiveness of a brace or orthosis to treat lateral compartment osteoarthritis or general osteoarthritis of the knee, or that compared a knee brace with a wedge insole, or that compared a brace or orthosis with operative treatment.
AUTHORS' CONCLUSIONS
Based on one brace study we conclude there is limited evidence that: a brace has additional beneficial effect (WOMAC, MACTAR, function tests) for knee osteoarthritis compared with medical treatment alone.(Silver) a sleeve has additional beneficial effect (WOMAC, function tests) for knee osteoarthritis compared with medical treatment alone.(Silver) a brace is more effective (WOMAC, function tests) than a neoprene sleeve.(Silver) Based on 3 orthoses studies, of which 2 were high quality, (n=2) we conclude there is limited evidence that: a laterally wedged insole decreases NSAID intake compared with a neutral insole. (Silver) patient compliance is better in the laterally wedged insole compared with a neutral insole. (Silver) a strapped insole has more adverse effects than a lateral wedge insole. (Silver). | 10.1002/14651858.CD004020.pub2 |
pubmed_547_6347 | Two novel d(10) metal coordination polymers [Zn(PDB)](n)() (1) and [Cd(3)(PDB)(2)(OH)(2)(H(2)O)(2)](n)() (2) (H(2)PDB = pyridine-3,4-dicarboxylic acid) have been synthesized under hydrothermal conditions and characterized by elemental analysis, IR, TG analysis, and single-crystal X-ray diffraction. Crystal data for 1: C(7)H(3)NO(4)Zn, orthorhombic Pna2(1), a = 8.423(17) A, b = 6.574(13) A, c = 12.899(3) A, Z = 4. Crystal data for 2: C(14)H(12)N(2)O(12)Cd(3), monoclinic C2/c, a= 20.130(4) A, b = 6.692(13) A, c = 13.081(3) A, beta = 102.78(3) degrees, Z = 4. Both compounds exhibit novel three-dimensional frameworks. Compound 1 not only possesses a one-dimensional rectangular channel but also contains infinite double-stranded helical chains. Compound 2 has two different types of channels, one being built up from pyridine rings and [CdO(5)N] and [CdO(6)] building units and the other being constructed from pyridine rings and [CdO(5)N] building units. Furthermore, both compounds show strong photoluminescence properties at room temperature. | 10.1021/ic035151s |
pubmed_687_21305 | Many airborne infectious diseases can be transmitted via exhaled contaminants transported in the air. Direct exposure occurs when the exhaled jet from the infected person directly enters the breathing zone of the target person. Indirect exposure occurs when the contaminants disperse in the room and are inhaled by the target person. This paper presents a simple method for differentiating the direct and indirect exposure to exhaled contaminants in mechanically ventilated rooms. Experimental data for 191 cases were collected from the literature. After analyzing the data, a simple method was developed to differentiate direct and indirect exposure in mixing and displacement ventilated rooms. The proposed method correctly differentiated direct and indirect exposure for 120 out of the 133 mixing ventilation cases and 47 out of the 58 displacement ventilation cases. Therefore, the proposed method is suitable for use at the early design stage to quickly assess whether there will be direct exposure to exhaled contaminants in a mechanically ventilated room. | 10.1007/s12273-018-0441-0 |
pubmed_822_15262 | Hepatitis A virus (HAV) infection is a major cause of acute hepatitis and occasionally leads to acute liver failure in both developing and developed countries. Although effective vaccines for HAV are available, the development of new antivirals against HAV may be important for the control of HAV infection in developed countries where no universal vaccination program against HAV exists, such as Japan. There are two forms of antiviral agents against HAV: direct-acting antivirals (DAAs) and host-targeting agents (HTAs). Studies using small interfering ribonucleic acid (siRNA) have suggested that the HAV internal ribosomal entry site (IRES) is an attractive target for the control of HAV replication and infection. Among the HTAs, amantadine and interferon-lambda 1 (IL-29) inhibit HAV IRES-mediated translation and HAV replication. Janus kinase (JAK) inhibitors inhibit La protein expression, HAV IRES activity, and HAV replication. Based on this review, both DAAs and HTAs may be needed to control effectively HAV infection, and their use should continue to be explored. | 10.14218/JCTH.2015.00016 |
pubmed_807_22817 | We study the calcium-induced vesicle release into the synaptic cleft using a deterministic algorithm and MCell, a Monte Carlo algorithm that tracks individual molecules. We compare the average vesicle release probability obtained using both algorithms and investigate the effect of the three main sources of noise: diffusion, sensor kinetics and fluctuations from the voltage-dependent calcium channels (VDCCs). We find that the stochastic opening kinetics of the VDCCs are the main contributors to differences in the release probability. Our results show that the deterministic calculations lead to reliable results, with an error of less than 20%, when the sensor is located at least 50 nm from the VDCCs, corresponding to microdomain signaling. For smaller distances, i.e. nanodomain signaling, the error becomes larger and a stochastic algorithm is necessary. | 10.1088/1478-3975/7/2/026008 |
pubmed_332_9695 | BACKGROUND
Several direct-acting antivirals for chronic hepatitis C virus (HCV) infection are available, but they are limited by tolerability and dosing schedules. Once-daily daclatasvir, a potent NS5A replication complex inhibitor, was generally well tolerated in phase 1 studies. We assessed daclatasvir in combination with pegylated interferon (peginterferon) and ribavirin for chronic HCV.
METHODS
In this double-blind, parallel-group, dose-finding, phase 2a study, treatment-naive patients with HCV genotype-1 infection (without cirrhosis) from 14 centres in the USA and France were randomly assigned (1:1:1:1) to receive peginterferon alfa-2a (180 μg per week) and ribavirin (1000-1200 mg daily) plus placebo or 3 mg, 10 mg, or 60 mg of daclatasvir taken once daily, for 48 weeks. The primary efficacy endpoint was undetectable HCV RNA at 4 weeks and 12 weeks after start of treatment (extended rapid virological response, eRVR). Analysis was of all participants who received one dose of study drug. We used descriptive analyses to compare results. This study is registered with ClinicalTrials.gov, number NCT00874770.
FINDINGS
48 patients were randomly assigned (12 per group); all received at least one dose of study drug. 15 patients discontinued treatment before week 48. Five of 12 patients (42%, 80% CI 22-64%) who received 3 mg daclatasvir achieved eRVR, compared with ten of 12 (83%, 61-96%) who received 10 mg daclatasvir, nine of 12 (75%, 53-90%) who received 60 mg daclatasvir, and one of 12 (8%, 1-29%) who received placebo. Adverse events and discontinuations as a result of adverse events occurred with similar frequency across groups.
INTERPRETATION
Daclatasvir seems to be a potent NS5A replication complex inhibitor that increases the antiviral potency of peginterferon and ribavirin. Our findings support the further development of regimens containing 60 mg daclatasvir for the treatment of chronic genotype-1 HCV infection.
FUNDING
Bristol-Myers Squibb. | 10.1016/S1473-3099(12)70138-X |
pubmed_328_4872 | Embedded medium-sized carbacycles and cyclohepta[b]indoles occur frequently as scaffold elements in natural products and bioactive compounds. Described herein is a conceptionally novel photochemically triggered cascade process to these scaffolds. Key to the cascading ring-expansion process is an unprecedented intramolecular alkyne analogue of the de Mayo reaction. | 10.1002/anie.201808578 |
pubmed_521_15827 | The prevalence of serum anti-DNA antibodies was evaluated by ELISA using oxidatively damaged DNA as antigen in 21 patients with systemic lupus erythematosus (SLE), in 9 spouses and in 15 first-degree relatives. These were compared with 12 healthy controls. There was no significant difference in the levels of serum antibodies detected between the group of spouses and normal controls with all results within the normal range of the assay. Binding of serum antibodies to the oxidatively damaged DNA was detectable in 12 (80%) of the relatives studied, and the range of values obtained overlapped significantly with the SLE patient group. The relevance of these antibodies to the immunopathology of SLE is unclear since they appear to be present in the absence of any clinical symptoms. However, they may be useful predictively as a marker for those individuals who are more likely to develop SLE. | 10.1016/0165-2478(94)90123-6 |
pubmed_132_15854 | PURPOSE
Many patients with benign prostatic hyperplasia (BPH) have storage symptoms. The aim of this study was to evaluate the effects of treatment with a 5-alpha reductase inhibitor (5ARI) on storage symptoms in patients with BPH.
METHODS
This study was conducted in 738 patients with lower urinary tract symptoms secondary to BPH. Patients with a prostate volume of higher than 30 mL on the transrectal ultrasound were classified into two groups: group A, in which an alpha blocker was solely administered for at least 12 months, and group B, in which a combination treatment regimen of an alpha blocker plus 5ARI was used. This was followed by an analysis of the changes in parameters such as the total International Prostate Symptom Score (IPSS), voiding symptom subscore, and storage symptom subscore between the two groups. In addition, we examined whether there was a significant difference between the two groups in the degree of change in storage symptoms between before and after the pharmacological treatment.
RESULTS
Of the 738 men, 331 had a prostate volume ≥30 mL, including 150 patients in group A and 181 patients in group B. Total IPSS, the voiding symptom subscore, and the storage symptom subscore were significantly lower after treatment than before treatment in both groups (P<0.05). A comparison of the degree of change between before and after treatment, however, showed no significant differences in the storage symptom subscore between the two groups (P>0.05).
CONCLUSIONS
Alpha blocker and 5ARI combination treatment is effective for patients with BPH including storage symptoms. However, 5ARI does not exert a significant effect on storage symptoms in BPH patients. | 10.5213/inj.2011.15.3.152 |
pubmed_1042_14000 | BACKGROUND
Fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DWI or DW-MRI) are tools for the diagnosis of pancreatic cancer. However, comparison of their diagnostic performance remains unknown.
PURPOSE
To indirectly compare the diagnostic value of DWI and FDG-PET/CT in the detection of pancreatic cancer.
MATERIAL AND METHODS
A literature search of PubMed, Embase, and Cochrane Library electronic databases for articles published through May 2018 yielded 875 articles. For the meta-analysis, we included 26 studies evaluating the efficacy of DWI and FDG-PET/CT for determining pancreatic cancer with a total of 1377 patients. QUADAS (Quality Assessment of Diagnostic Accuracy Studies) was used to assess the study quality. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curves (AUC) with their 95% confidence intervals were calculated for each individual study.
RESULTS
There were no significant differences between DWI and FDG-PET/CT for sensitivity, specificity, PLR, NLR, or DOR, while DWI AUC was higher than that of FDG-PET/CT for the detection of pancreatic cancer.
CONCLUSION
The diagnostic value of both DWI and FDG-PET/CT were comparable and, hence, both techniques seem to be equally useful tools for the diagnosis of pancreatic cancer. | 10.1177/0284185120907246 |
pubmed_506_19272 | BACKGROUND
Children who experience neglect and abuse are likely to have impaired brain development and entrenched learning deficiencies. Early years interventions such as intensive education and care for these children are known to have the potential to increase their human capital. The Early Years Education Program (EYEP) is a new program offered by the Children's Protection Society (CPS) in Melbourne, Australia. EYEP is targeted at the needs of children who have been or are at risk of being abused or neglected. It has the dual focus of seeking to address the consequences of abuse and neglect on children's brain development and redressing their learning deficiencies. Our objective is to determine whether EYEP can improve school readiness by conducting a randomised controlled trial (RCT) of its impacts.
METHODS/DESIGN
The RCT is being conducted with 90 participants (45 intervention and 45 control). Eligible children must be aged under three years and assessed as having two or more risk factors as defined in the Department of Human Services Best Interest Case Practice Model. The intervention group participate for three years (or until school entry) in EYEP. The trial does not provide any early years education or care to the control group. Data are being collected on outcome measures for participants in EYEP and the control group at the baseline, at yearly intervals for three years, and six months after commencing the first year of school. Outcome measures encompass children's health and development, academic ability and emotional and behavioural regulation; and quality of parenting practices. The study will evaluate the impact of EYEP on these outcomes, and undertake a benefit-cost analysis of the program.
DISCUSSION
Findings from the study have the potential to influence the quality of care and education for the large population of children in Australia who are at risk of abuse and neglect, as well as for children in mainstream childcare. The study will provide up-to-date evidence on the impact of an early years intervention relevant to an urban population in Australia; as well as (to our knowledge) being the first RCT of an early years education and care intervention in Australia.
TRIAL REGISTRATION
ACTRN 12611000768998. Date 22nd July 2011. | 10.1186/1471-2458-14-965 |
pubmed_497_19377 | Patients treated with L-asparaginase may present with hemorrhagic and thrombotic cerebrovascular events. This syndrome generally occurs after a few weeks of therapy and may occur after L-asparaginase therapy is completed. Complications appear to result from depletion of plasma proteins involved in coagulation and fibrinolysis. Seizures are uncommon symptoms, and are always caused by cerebrovascular events. We report a case of seizure associated with L-asparaginase therapy but no evidence of hemorrhagic or thrombotic cerebrovascular events. | 10.1177/107602960000600409 |
pubmed_419_22917 | BACKGROUND
Locoregional failure is a unique and challenging problem in head and neck cancer with controversy surrounding the use of re-irradiation in the treatment. We aimed to evaluate the dosimetry and technical parameters in utilizing a collagen matrix with embedded Cesium-131 (Cs-131) radioactive isotope seeds as it relates to dose distribution and dose to carotid artery.
METHODS AND MATERIALS
Cadaveric feasibility study randomizing Cs-131 strands alone or Cs-131 with collagen matrix to be placed into neck dissection defects. For the dose computation, physicists employed the TG-43 dosimetry calculation algorithm with a point source assumption to compute the dose. Carotid arteries were contoured in MIM-Symphony software and the carotid artery maximum and mean doses were calculated in accordance with TG-43 specifications. Ease of use of collagen matrix tiles on a 7-point Likert scale and mean radiation dose to the carotid artery.
RESULTS
Ease of use score was higher in collagen matrix compared to stranded seeds with a mean score of 6.3 +/- 1.2 compared to 4.5 +/- 0.87. Time of implantation was statistically significantly, p = 0.031, lower in the collagen matrix group (M = 5.17 min, SD = 4.62) compared to stranded seeds (M = 15.83 min, SD = 3.24). Mean radiation dose to the carotid artery was 62.8 Gy +/- 9.46 in the collagen matrix group compared to 108.2 Gy +/- 55.6 in the traditional Cs-131 seeds group.
CONCLUSIONS
We present a feasibility and concept cadaveric study using a collagen matrix with Cesium-131 demonstrating preliminary evidence to support its ease of use, decreased time to implantation, and decreased dose delivered to the carotid artery. | 10.1016/j.brachy.2022.09.160 |
pubmed_786_1800 | The inoculation of 2000 colony-forming units of Corynebacterium pseudotuberculosis into one teat canal of each of three cows resulted in severe, chronic, pyogranulomatous mastitis. Within three days the cows had a reduced haematocrit, haemoglobin concentration and red cell count. The anaemia was initially normocytic, normochromic and non-regenerative, and was associated with a brief peak of neutrophilia; a regenerative response became evident two to three weeks later. Clinical signs of mastitis appeared seven to 14 days after the inoculation, with a peak of high fever, more severe anaemia, a second peak of neutrophilia and the complete cessation of milk production from all quarters; extensive and severe pyogranulomatous mastitis developed in the inoculated quarters. No other lesions were detected postmortem, and C pseudotuberculosis was cultured from the affected quarters but not from the supramammary lymph nodes and viscera. | pubmed_786_1800 |
pubmed_118_24818 | In plants, pollination syndromes (the correlated presence of many features of relevance to pollination mode, for instance pollination by a particular animal clade) are a striking feature of plant biodiversity, providing great floral phenotypic diversity (Fenster et al. ). Adaptation to a particular animal pollinator provides an explanation for why recently diverged plants can have such extreme differentiation in floral form. One might expect such elaborate adaptations to provide a high degree of pollinator specificity and hence reproductive isolation, but there are many cases where substantial gene flow exists between extreme floral morphs (see Table 1), and the resulting hybrids may be highly fertile. This gene flow provides tremendous opportunities to study the genetics and biology of the pollination syndromes by providing intermediate forms and segregating genotypes. If it is true that pollination syndromes result from adaptation under strong selection, we will expect such flowers to be crucibles of natural selection. If strong selection for particular floral phenotypes can be shown, then this, when coupled with hybridization, will give us one of the most valuable of all experimental systems for evolutionary research: gene flow and selection in balance. In this issue of Molecular Ecology, the paper of Milano et al. () delivers this. It shows that in populations of the Ipomopsis aggregata complex, gene flow between pollination morphs is high and selection to stabilize those morphs is also high: a probable case of gene flow-selection balance. | 10.1111/mec.13903 |
pubmed_594_7713 | Malate dehydrogenase from Escherichia coli is highly specific for the oxidation of malate to oxaloacetate. The technique of site-specific modulation has been used to alter the substrate binding site of this enzyme. Introduction of a cysteine in place of the active site binding residue arginine 153 results in a mutant enzyme with diminished catalytic activity, but with K(m) values for malate and oxaloacetate that are surprisingly unaffected. Reaction of this introduced cysteine with a series of amino acid analog reagents leads to the incorporation of a range of functional groups at the active site of malate dehydrogenase. The introduction of a positively charged group such as an amine or an amidine at this position results in improved affinity for several inhibitors over that observed with the native enzyme. However, the recovery of catalytic activity is less dramatic, with less than one third of the native activity achieved with the optimal reagents. These modified enzymes do have altered substrate specificity, with alpha-ketoglutarate and hydroxypyruvate no longer functioning as alternative substrates. | 10.1074/jbc.M100892200 |
pubmed_611_764 | The overall improvement in the health of Americans over the 20th century is best exemplified by dramatic changes in 2 trends: 1) the age-adjusted death rate declined by about 74%, while 2) life expectancy increased 56%. Leading causes of death shifted from infectious to chronic diseases. In 1900, infectious respiratory diseases accounted for nearly a quarter of all deaths. In 1998, the 10 leading causes of death in the United States were, respectively, heart disease and cancer followed by stroke, chronic obstructive pulmonary disease, accidents (unintentional injuries), pneumonia and influenza, diabetes, suicide, kidney diseases, and chronic liver disease and cirrhosis. Together these leading causes accounted for 84% of all deaths. The size and composition of the American population is fundamentally affected by the fertility rate and the number of births. From the beginning of the century there was a steady decline in the fertility rate to a low point in 1936. The postwar baby boom peaked in 1957, when 123 of every 1000 women aged 15 to 44 years gave birth. Thereafter, fertility rates began a steady decline. Trends in the number of births parallel the trends in the fertility rate. Beginning in 1936 and continuing to 1956, there was precipitous decline in maternal mortality from 582 deaths per 100 000 live births in 1935 to 40 in 1956. Since 1950 the maternal mortality ratio dropped by 90% to 7.1 in 1998. The infant mortality rate has shown an exponential decline during the 20th century. In 1915, approximately 100 white infants per 1000 live births died in the first year of life; the rate for black infants was almost twice as high. In 1998, the infant mortality rate was 7.2 overall, 6.0 for white infants, and 14.3 for black infants. For children older than 1 year of age, the overall decline in mortality during the 20th century has been spectacular. In 1900, >3 in 100 children died between their first and 20th birthday; today, <2 in 1000 die. At the beginning of the 20th century, the leading causes of child mortality were infectious diseases, including diarrheal diseases, diphtheria, measles, pneumonia and influenza, scarlet fever, tuberculosis, typhoid and paratyphoid fevers, and whooping cough. Between 1900 and 1998, the percentage of child deaths attributable to infectious diseases declined from 61.6% to 2%. Accidents accounted for 6.3% of child deaths in 1900, but 43.9% in 1998. Between 1900 and 1998, the death rate from accidents, now usually called unintentional injuries, declined two-thirds, from 47. 5 to 15.9 deaths per 100 000. The child dependency ratio far exceeded the elderly dependency ratio during most of the 20th century, particularly during the first 70 years. The elderly ratio has gained incrementally since then and the large increase expected beginning in 2010 indicates that the difference in the 2 ratios will become considerably less by 2030. The challenge for the 21st century is how to balance the needs of children with the growing demands for a large aging population of elderly persons. | 10.1542/peds.106.6.1307 |
pubmed_77_14795 | Certain variables in the preparation of chromosome suspensions for flow cytometric analysis have been investigated. The optimal conditions have been determined. The results of this series of experiments have been incorporated to yield a preparation protocol that gives chromosome profiles with a low amount of small particle debris and few chromosome clumps. The method reduces variability that results from sample preparation. Chromosomes are optimally isolated in a hypotonic solution buffered to pH 8.0. MgSO4 and dithiothreitol added to the buffer reduce the number of clumps and small fluorescent particles. The presence of MgSO4 also stabilizes the chromosomes and precludes the need for other stabilizing agents such as propidium iodide. When the swelling buffer developed in this investigation is used, unstained chromosomes are stable for at least 1 wk if stored at 4 degrees C. The preparation procedure can be used with the DNA stains, propidium iodide, Hoechst 33258, and mithramycin. Preliminary experiments show that this procedure can also be used for bivariate analysis of human and Chinese hamster chromosomes. The importance of this improvement for studies on chromosome damage caused by irradiation or mutagens is discussed. | 10.1002/cyto.990050203 |
pubmed_774_4024 | This study determined effects of different black pepper levels (5, 10 or 15 g kg-1), sodium ascorbate usage and cooking level (raw, medium, medium well and well done) on nitrosamine formation in sucuk (a kind of dry fermented sausage). Sodium ascorbate decreased residual nitrite considerably. Cooking level had a very significant effect on nitrosodimethylamine (NDMA), nitrosopyrrolidine (NPYR) and nitrosopiperidine (NPIP) contents. NPIP content increased in sucuk both with and without ascorbate, as cooking level increased. High black pepper level decreased NPIP content in both raw and well done samples. The use of 15 g kg-1 black pepper level caused an increase in both NDMA and NPYR contents in the absence of ascorbate. In contrast, the combination of ascorbate and 15 g kg-1 black pepper resulted in a decrease in NPYR. | 10.1016/j.foodchem.2019.02.129 |
pubmed_994_4322 | The ocular surface is exposed to many chronic inflammatory stimuli, and goblet cell hyperplasia of the conjunctiva occurs in many situations. We report two cases of epithelial goblet cell hyperplasia with nonspecific chronic inflammation which occurred on the internal canthus of elderly people. These cases shared the same clinicopathological features that mimicked neoplastic lesion macroscopically, but are composed of nonspecific inflammatory changes pathologically. Immunostaining of the tissue showed few IgG4+ plasma cells, and no neoplastic changes were observed. Both cases arose in elderly patients over the age of 80 years. Pathogenesis and clinical significance of the lesion is unclear, but it might be age related. Recognition of this diagnosis might help us avoid overdiagnosis of malignancy and to reach the correct diagnosis. | 10.1007/s10792-015-0083-5 |
pubmed_844_17430 | The skeletal responses to calcium depletion and repletion in rodents have been well characterized, but those in humans are poorly understood. The present study sought to evaluate the effects of short term dietary calcium depletion and repletion on biochemical markers of bone turnover in 15 young Caucasian women (age, 21-30 yr). The study contained 3 phases: 1) 5 days of a regular diet containing more than 800 mg/day calcium to establish baseline values (baseline phase), 2) 22 days of a restricted diet containing less than 300 mg/day calcium (depletion phase), and 3) 7 days of a normal diet containing more than 800 mg/day calcium (repletion phase). Serum and urine samples were obtained from each subject during the baseline phase; on the first, second, and last days of the depletion phase; and on the third and last days of the repletion phase. Serum levels of calcium, PTH, 1,25-dihydroxyvitamin D3, osteocalcin, and C-terminal type I procollagen peptide (PICP) and urinary levels of calcium and deoxypyridinoline were determined. Serum and urinary calcium levels were significantly reduced, and serum PTH and 1,25-dihydroxyvitamin D3 levels were markedly increased during depletion. These changes were completely reversed after 1 week of repletion. Depletion also rapidly and significantly increased the urinary deoxypyridinoline level, indicating increased bone resorption. The increase also returned rapidly to baseline upon repletion. Calcium depletion had contrasting effects on bone formation markers; whereas depletion significantly reduced the serum PICP level, it significantly increased serum osteocalcin level. Past histomorphometric studies in rodents indicated that the number of mature but inactive osteoblasts was increased during depletion despite an inhibition of bone formation. Thus, it is speculated that although the reduction in serum PICP reflected the depletion-associated inhibition of bone formation, the increase in serum osteocalcin could represent this depletion-related increase in osteoblast number. During repletion, serum osteocalcin remained elevated above baseline. PICP recovered from its depressed level and increased above baseline, a finding consistent with past histomorphometric findings of increased bone formation during repletion. In summary, this study confirms that 1) a short calcium depletion period produces calcium stress in young women, which leads to rapid stimulation of bone resorption and inhibition of bone formation; and 2) a subsequent calcium repletion period could lead to a compensatory increase in bone formation. In conclusion, the skeletal responses to calcium depletion/ repletion in young women may be similar to those in rodents. | 10.1210/jcem.83.6.4891 |
pubmed_960_8261 | The role of intrauterine insemination as treatment for specific factor of infertility and for empiric treatment in idiopathic infertility is hereby described. A review of the different prerequisite evaluations is presented: ovarian age, pelvis evaluation and implantation parameters and negative lifestyle (woman weight and toxics). The efficiency of the treatment as evaluated by different studies is described in terms of pregnancy rate and obstetrical and perinatal outcome. In 2004, the treatment of idiopathic infertility by insemination/ovulation induction is challenged in the face of prevention of multiple pregnancies. | 10.1016/j.gyobfe.2004.07.016 |
pubmed_170_4909 | In decerebrated rats, we determined the pressor and cardioaccelerator reflex responses to static contraction of hindlimb muscles whose femoral arteries were either occluded 72 h before contraction, occluded 3 min before contraction, or freely perfused. We found that the pressor reflex arising from the limb whose femoral artery was occluded for 72 h before contraction (32 +/- 5 mmHg, n = 16) was significantly higher than the pressor reflex arising from the contralateral freely perfused limb (15 +/- 3 mmHg, n = 16, P < 0.001) or than that arising from the contralateral limb whose femoral artery was occluded for only 3 min (17 +/- 4 mmHg, n = 16, P < 0.001). Moreover, the pressor reflex arising from the limb whose femoral artery was occluded for 3 min before the start of contraction was not significantly different than that arising from the contralateral freely perfused limb (n = 16, P = 0.819). The pressor component of the reflex arising from the limb whose femoral artery was occluded for 72 h was not changed by transient receptor potential vanilloid (TRPV) 1 receptor blockade with iodo-resiniferatoxin (n = 15, P = 0.272), although the cardioaccelerator component was significantly reduced (P = 0.005). In addition, the pressor response evoked by capsaicin injection in the femoral artery of the 72-h occluded limb was more than double that evoked from the freely perfused limb (P = 0.026). We conclude that chronic (i.e., 72 h) but not acute (3 min), femoral arterial occlusion augments pressor reflex arising from contraction of hindlimb muscles and that TRPV1 receptors play little role in this augmentation. | 10.1152/ajpheart.00141.2010 |
pubmed_1141_21720 | In order to evaluate the combined effect of Amifostine and Merocyanine 540 during photoirradiation in neoplastic cells, bone marrow cells from children with acute leukemia (AL), age-matched controls as well as HL-60 cell line were studied. Cell suspensions were incubated with Amifostine, then with MC 540 and they were subsequently exposed to different irradiation doses by Argon Laser 514 nm. Cell survival was estimated by trypan blue supravital stain following a 24-h incubation. The leukemic cell line was studied in continuous liquid cell cultures for 4 weeks. The survival of normal bone marrow progenitors has been estimated by colony formation assay in methylcellulose cultures. Our results showed that Amifostine enhances the photokilling effect of MC 540 on leukemic cells and significantly protects bone marrow nucleated and committed progenitors (BFU-E and CFU-GM) from children with AL under chemotherapy. In conclusion, Amifostine seems to be a promising cytoprotective agent in the clinical use of purging with MC 540 mediated phototherapy. | 10.1016/s0145-2126(99)00202-7 |
pubmed_203_12728 | H2AX is a histone variant that is systematically found and ubiquitously distributed throughout the genome. Since it has been reported that DNA double-strand breaks (DSBs) induce phosphorylation of H2AX at serine 139 (gammaH2AX), an immunocytochemical assay with antibodies recognizing gammaH2AX has become the gold standard for the detection of DSBs. This assay is quite sensitive and is a specific indicator for the existence of a DSB. Until now, it has been reported that various kinds of physical, chemical, and biological factors induce the formation of the gammaH2AX foci detected using this assay. Even when gammaH2AX foci were detected, it was not always possible to conclude that the detected DSBs were produced by environmental stresses in the absence of any known radiation. In this review, emphasis is on discussing whether gammaH2AX foci formation depends on the formation of DSBs. | 10.1016/j.canlet.2005.07.016 |
pubmed_359_6396 | Airflow obstruction in chronic airway disease is associated with airway and pulmonary vascular remodeling, of which the molecular mechanisms are poorly understood. Paracrine actions of angiogenic factors released by resident or infiltrating inflammatory cells following activation by proinflammatory cytokines in diseased airways could play a major role in the airway vascular remodeling process. Here, the proinflammatory cytokines interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha were investigated on cell cultures of human airway smooth muscle (ASM) for their effects on mRNA induction and protein release of the angiogenic peptide, vascular endothelial growth factor (VEGF). IL-1beta (0.5 ng/mL) and TNF-alpha (10 ng/mL) each increased VEGF mRNA (3.9 and 1.7 kb) expression in human ASM cells, reaching maximal levels between 16 and 24 and 4 and 8 h, respectively. Both cytokines also induced a time-dependent release of VEGF, which was not associated with increased ASM growth. Preincubation of cells with 1 microM dexamethasone abolished enhanced release of VEGF by TNF-alpha. The data suggest that human ASM cells express and secrete VEGF in response to proinflammatory cytokines and may participate in paracrine inflammatory mechanisms of vascular remodeling in chronic airway disease. | 10.1385/CBB:43:1:119 |
pubmed_35_15286 | The interaction of the TATA-box binding protein from the thermophilic and halophilic archaea Pyrococcus woesei (PwTBP) with an oligonucleotide containing a specific binding site is stable over a very broad range of temperatures and ionic strengths, and is consequently an outstanding system for characterising general features of protein-DNA thermodynamics. In common with other specific protein-DNA recognition events, the PwTBP-TATA box interaction is accompanied by a large negative change in heat capacity (deltaCp) arising from the total change in solvation that occurs upon binding, which in this case involves a net uptake of cations. Contrary to previous hypotheses, we find no overall effect of ionic strength on this heat capacity change. We investigate the local contributions of site-specific ion and water binding to the overall change in heat capacity by means of a series of site-directed mutations of PwTBP. We find that although changes in the local ion binding capacity affect the enthalpic and entropic contributions to the free energy of the interaction, they do not affect the change in heat capacity. In contrast, we find remarkably large heat capacity effects arising from two particular symmetry-related mutations. The great magnitude of these effects is not explicable in terms of current semi-empirical models of heat capacity change. Previously reported X-ray crystal structures show that these mutated residues are at the centre of an evolutionarily conserved network of water-mediated hydrogen bonds between the protein and the DNA backbone. Consequently, we conclude that, in addition to water molecules buried in the protein-DNA interface that have been previously shown to influence heat capacity, bridging water molecules in a highly polar surface environment can also contribute substantially to negative heat capacity change on formation of a protein-DNA complex. | 10.1016/j.jmb.2003.12.061 |
pubmed_434_1317 | A large body of evidence has established the role of the medial preoptic area (mPOA) in regulation of slow wave sleep (SWS). Although the mPOA neurons contain excitatory neurotransmitter glutamate, its role in sleep-wakefulness is not known. In the present study microinjection of monosodium glutamate (40, 80 and 120 ng) into the mPOA augmented SWS. Earlier reports have shown enhancement of paradoxical sleep by glutamate in other brain areas. | 10.1016/j.bbr.2010.11.007 |
pubmed_739_3435 | Eight patients with Waardenburg's syndrome (WS) with normal hearing and 3 additional patients exhibiting a low-frequency hearing loss were tested for the level of the acoustic distortion product 2f1-f2 by means of the Otodynamics Distortion Product Analyser (ILO92). Wide notches in distortion product otoacoustic emissions (DPOAEs) between 1,000 and 3,000 Hz were found in 7 (12 ears, 87.5%) examined patients with normal audiograms, which was a significantly higher rate than that found in the control group (10%). The 3 patients with low-frequency hearing loss a gave a consistent pattern in audiometric configuration shown by both pure tone audiograms and DPOAEs. It is concluded from these initial results that DPOAEs may be a useful approach to identifying subclinical pathologic aberrations in the inner ear in WS patients, and may be a predictor of low-frequency sensorineural hearing loss. | 10.1177/000348949710600307 |
pubmed_857_1492 | OBJECTIVE
To test the hypothesis that the induction and maintenance of brain death leads to a decrease in myocardial contractility.
DESIGN
Prospective, randomized, controlled trial.
SETTING
Laboratory at a large, university-affiliated medical center.
SUBJECTS
Sixteen adult, male, mongrel dogs weighing 15 to 25 kg.
INTERVENTIONS
Myocardial contractile performance was evaluated after the induction of either brain death (n = 8), sham brain death (n = 4), or an operative procedure serving as a time control (n = 4). Brain death was induced by increasing and maintaining intracranial pressure above arterial systolic pressure. Contractile performance was determined with sonomicrometers arrayed to measure wall thickness in the anterior and posterolateral left ventricle. Brief aortic constrictions enabled derivation of the end-systolic pressure-thickness relationship, a relatively load-insensitive index of contractility.
MEASUREMENTS AND MAIN RESULTS
No statistically significant hemodynamic differences were detected between the sham and time control groups. The brain-dead group displayed marked hemodynamic deterioration; 4 hrs after brain death was induced, mean arterial blood pressure, cardiac index, and the peak positive first derivative of left ventricular pressure were 63%, 35%, and 53% lower, respectively, than those values in the two control groups. However, the slope of the end systolic pressure-thickness relationship remained at 92 +/- 12% of baseline levels 4 hrs after brain death was induced and was not significantly different from the two control groups.
CONCLUSIONS
The hemodynamic deterioration after the induction of brain death could not be attributed to a decrease of myocardial contractility as measured by the end systolic pressure-thickness relationship. | 10.1097/00003246-199311000-00024 |
pubmed_621_23871 | OBJECTIVE
In the general population, a low ankle-brachial index (ABI) (<0.9) is strongly associated with (cardiovascular) mortality. However, the association between the ABI and mortality may be weaker in individuals with diabetes, as ankle pressures may be elevated by medial arterial calcification and arterial stiffening, which occur more frequently in diabetes. Therefore, the aim of this study was to compare the association between ABI and mortality in individuals without and with diabetes.
RESEARCH DESIGN AND METHODS
We studied the associations between ABI and cardiovascular and all-cause mortality in 624 individuals from the Hoorn study, a population-based cohort of 50- to 75-year-old individuals (155 with diabetes and 469 without) followed for a median period of 17.2 years. Data were analyzed using Cox proportional hazards models.
RESULTS
During the follow-up period, 289 of 624 (46.3%) participants died (97 of 155 with and 192 of 469 without diabetes and 52 of 65 with and 237 of 559 without ABI <0.9): 85 (29.4%) of CVD (30 of 155 with and 55 of 469 without diabetes and 20 of 65 with and 65 of 559 without ABI <0.9). A low ABI was strongly associated with cardiovascular mortality (relative risk 2.57 [95% CI 1.50-4.40]) and all-cause mortality (2.02 [1.47-2.76]), after adjustment for Framingham risk factors. The associations of the ABI with mortality did not differ between individuals without and with diabetes for cardiovascular (P(interaction) = 0.45) or all-cause (P(interaction) = 0.63) mortality.
CONCLUSIONS
In the Hoorn Study, associations between ABI and cardiovascular and all-cause mortality were similar in individuals without and with diabetes. Future studies should investigate, in both individuals without and with diabetes, whether measurement of ABI can be used to guide treatment decisions. | 10.2337/dc12-0178 |
pubmed_337_12866 | BACKGROUND
Several clinical studies have indicated the efficacy of cilostazol, a selective inhibitor of phosphodiesterase 3, in preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). They were not double-blinded trial resulting in disunited results on assessment of end points among the studies. The randomized, double-blind, placebo-controlled study was performed to assess the effectiveness of cilostazol on cerebral vasospasm.
METHODS
Patients with aneurysmal SAH admitted within 24 h after the ictus who met the following criteria were enrolled in this study: SAH on CT scan was diffuse thick, diffuse thin, or local thick, Hunt and Hess score was less than 4, administration of cilostazol or placebo could be started within 48 h of SAH. Patients were randomly allocated to placebo or cilostazol after repair of a ruptured saccular aneurysm by aneurysmal neck clipping or endovascular coiling, and the administration of cilostazol or placebo was continued up to 14 days after initiation of treatment. The primary end point was the occurrence of symptomatic vasospasm (sVS), and secondary end points were angiographic vasospasm (aVS) evaluated on digital subtraction angiography, vasospasm-related new cerebral infarction evaluated on CT scan or MRI, and clinical outcome at 3 months of SAH as assessed by Glasgow Outcome Scale, in which poor outcome was defined as severe disability, vegetative state, and death. All end points were evaluated with blinded assessment.
RESULTS
One hundred forty eight patients were randomly allocated to the cilostazol group (n = 74) or the control group (n = 74). The occurrence of sVS was significantly lower in the cilostazol group than in the control group (10.8 vs. 24.3%, p = 0.031), and multiple logistic analysis showed that cilostazol use was an independent factor reducing sVS (OR 0.293, 95% CI 0.099-0.568, p = 0.027). The incidence of aVS and vasospasm-related cerebral infarction were not significantly different between the groups. Poor outcome was significantly lower in the cilostazol group than in the control group (5.4 vs. 17.6%, p = 0.011), and multiple logistic analyses demonstrated that cilostazol use was an independent factor that reduced the incidence of poor outcome (OR 0.221, 95% CI 0.054-0.903, p = 0.035). Severe adverse events due to cilostazol administration did not occur during the study period.
CONCLUSIONS
Cilostazol administration is effective in preventing sVS and improving outcomes without severe adverse events. A larger-scale study including more cases was necessary to confirm this efficacy of cilostazol. | 10.1159/000445509 |
pubmed_937_13751 | The effect of hydrocortisone on functional activity of peripheral blood lymphocytes in different vertebrates during ontogeny was studied by the blast transformation test. Hydrocortisone in a dose of 100 mg/kg inhibited functional activities of T and B lymphocytes in vitro stimulated by mitogens. This inhibitory effect was observed in both young and adult animals. However proliferative activity of concanavalin A-dependent blood T suppressors in rats increased, especially in adult animals (by 3.5 times). Hence, hydrocortisone produced different effects on functional activity of peripheral blood lymphocytes in the studied species, and these effects are dose- and species-dependent. | 10.1023/a:1019813805190 |
pubmed_494_17189 | The present paper compares the arsenic removal capacities of three bacterial strains namely, Ralstonia eutropha MTCC 2487, Pseudomonas putida MTCC 1194 and Bacillus indicus MTCC 4374 form wastewater (simulated acid mine drainage) containing arsenic (As(III):As(V)::1:1), Fe, Mn, Cu and Zn in the concentration of 15 mg/l, 10 mg/l, 2 mg/l, 5 mg/l and 10 mg/l respectively, in bulk liquid phase. Growth patterns of these bacteria in presence of arsenic in solution as well as under starvation have also been investigated as the acid mine drainage normally does not contain organic carbon and also contains high arsenic. At the nutrient broth concentration of 1.25 g/l and in presence of 15 mg/l arsenic sufficient growth of these strains have been observed. However, growth of Ralstonia eutropha MTCC 2487 has been found slightly more than Pseudomonas putida MTCC 1194 and Bacillus indicus MTCC 4374. Arsenic removal capacities of Ralstonia eutropha MTCC 2487, Pseudomonas putida MTCC 1194 and Bacillus indicus MTCC 4374 from simulated acid mine drainage are approximately 67%, 60% and 61% respectively. It has also been observed that arsenic concentration of 15 mg/l prolongs the stationary phase of these strains. pH and temperature for the above studies have been maintained at 7.1 +/- 0.1 and 29 +/- 1 degrees C, respectively. | 10.1002/jobm.200800084 |
pubmed_743_23540 | Biofortified foods are a new approach to increase minerals in the diet, and evidence suggests that zinc (Zn) biofortification can improve Zn physiological status in humans. This systematic review aimed to answer the question: "What are the effects of the consumption of Zn biofortified foods on Zn status in humans?". This review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD42021250566). PubMed, Cochrane, Scopus and Science Direct databases were searched for studies that evaluated the effects of Zn biofortified foods on Zn absorption. Of 4282 articles identified, nine remained after inclusion/exclusion criteria were applied. Limitations in study quality, external and internal validity (bias/confounding), and study power were evaluated. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. Of the nine articles included, five observed an increase in total Zn absorption, and one showed that Zn participated in the conversion of linoleic acid to dihomo-γ-linolenic acid. By increasing the amount of Zn in the food, Zn biofortification can reduce the phytate:Zn molar ratio and improve Zn absorption in humans. More studies are needed to clarify what portion of Zn biofortified foods/day is needed to achieve a significant effect on Zn status. | 10.1080/10408398.2021.2010032 |
pubmed_300_15097 | We seek an explanation for the neurophysiological phenomenon of event-related desynchronization (ERD) by using models of diffusively coupled nonlinear oscillators. We demonstrate that when the strength of the event is sufficient, ERD is found to emerge and the accomplishment of a behavioral or functional task is determined by the nature of the desynchronized state. We illustrate the phenomenon for the case of limit cycle and chaotic systems. We numerically demonstrate the occurrence of ERD and provide an analytical explanation. We also discuss possible applications of the observed phenomenon in real physical systems other than the brain. | 10.1103/PhysRevLett.103.074101 |
pubmed_1007_1772 | Mannitol is often added to the cardiopulmonary bypass pump prime to reduce the incidence of renal dysfunction, but studies so far have been inconclusive. Urinary excretion of microalbumin and retinol binding protein are more sensitive than routine biochemical tests of renal function after cardiac surgery. We performed a double-blind, randomised, controlled trial in cardiac surgical patients with pre-operative plasma creatinine < 130 micromol x l(-1). Twenty patients received 0.5 g x kg(-1) of mannitol in the pump prime, whereas 20 control patients received an equivalent volume of Hartmann's solution. Blood and urine samples were taken on the day before surgery and daily for 5 days postoperatively for measurement of plasma urea and creatinine, urinary creatinine, retinol binding protein and microalbumin. We found no differences between the mannitol and control patients for any measured variable, and conclude that mannitol has little impact on renal function in patients with normal pre-operative plasma creatinine concentrations. | 10.1111/j.1365-2044.2008.05540.x |
pubmed_828_14052 | BACKGROUND
Nonviral gene therapy requires a high yield and a low cost production of eukaryotic expression vectors that meet defined criteria such as biosafety and quality of pharmaceutical grade. To fulfil these objectives, we designed a novel antibiotic-free selection system.
METHODS
The proposed strategy relies on the suppression of a chromosomal amber mutation by a plasmid-borne function. We first introduced a nonsense mutation into the essential Escherichia coli thyA gene, resulting in thymidine auxotrophy. The bacterial strain was optimized for the production of small and novel plasmids free of antibiotic resistance markers (pFARs) and encoding an amber suppressor t-RNA. Finally, the potentiality of pFARs as eukaryotic expression vectors was assessed by monitoring luciferase activities after electrotransfer of LUC-encoding plasmids into various tissues.
RESULTS
The introduction of pFARs into the optimized bacterial strain restored normal growth to the auxotrophic mutant and allowed an efficient production of monomeric supercoiled plasmids. The electrotransfer of LUC-encoding pFAR into muscle led to high luciferase activities, demonstrating an efficient gene delivery. In transplanted tumours, transgene expression levels were superior after electrotransfer of the pFAR derivative compared to a plasmid carrying a kanamycin resistance gene. Finally, in skin, whereas luciferase activities decreased within 3 weeks after intradermal electrotransfer of a conventional expression vector, sustained luciferase expression was observed with the pFAR plasmid.
CONCLUSIONS
Thus, we have designed a novel strategy for the efficient production of biosafe plasmids and demonstrated their potentiality for nonviral gene delivery and high-level transgene expression in several tissues. | 10.1002/jgm.1441 |
pubmed_938_8309 | The paper deals with the direct experimental proof that human immunoglobulin G1 (IgG1) contains a reactive disulfide bond that can be opened by 3,3'-dithiobis(6-nitrobenzoate) (DTNB) within 24 h by a SH-catalysed disulfide exchange reaction. These results were obtained with the purified IgG1 myeloma protein and confirm earlier indirect evidence based on correlation analysis of DTNB reactivity and quantitative IgG1 determination. The reactive disulfide bond is most likely the one between Cys235 of the heavy chains in the "hinge"-region, activated for the disulfide exchange by the protonated amino groups of Lys231 as turned out by analysis of IgG1. As with the whole molecule, one mol of reactive disulfide was found per mol of the Fc-fragment. 0.8 mol of labile S-S bonds was detected per mol of F(ab)2. After separation of the excess of reagent, the sedimentation pattern still corresponded with the dimer. The unaltered antigenic properties as well as the crystallizability speak against any severe conformational changes. Therefrom it was concluded that in approximately 80% of the F(ab)2 molecules one of the two inter heavy chain-bridges was opened. With the isolated F(ab)-fragment a reaction with DTNB was ascertained to an extent of 20%, which is probably due to an altered stability of the heavy-light chain-SS-bridge. However, no influence on the sedimentation pattern was observed. The intrachainar disulfide bonds of neither the heavy nor the light chain reacted with DTNB to a measurable extent. | pubmed_938_8309 |
pubmed_496_14289 | We study Poincaré recurrence of chaotic attractors for regions of finite size. Contrary to the standard case, where the size of the recurrent regions tends to zero, the measure is no longer supported solely by unstable periodic orbits of finite length inside it, but also by other special recurrent trajectories, located outside that region. The presence of the latter leads to a deviation of the distribution of the Poincaré first return times from a Poissonian. Consequently, by taking into account the contribution of these special recurrent trajectories, a corrected estimate of the measure is obtained. This has wide experimental implications, as in the laboratory all returns can exclusively be observed for regions of finite size, and only unstable periodic orbits of finite length can be detected. | 10.1103/PhysRevLett.95.094101 |
pubmed_699_16111 | INTRODUCTION
Axicabtagene ciloleucel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that was recently approved for relapsed or refractory follicular lymphoma following progression on two or more lines of therapy including an anti-CD20 monoclonal antibody with an alkylating agent, providing a therapeutic breakthrough in a subset of indolent non-Hodgkin lymphoma associated with poor clinical outcomes.
AREAS COVERED
In this article, we outline the drug profile of axicabtagene ciloleucel in comparison to currently approved agents and other CAR T-cell and T-cell redirecting therapies under investigation for the treatment of relapsed or refractory follicular lymphoma. We also review the efficacy, safety, and pharmacokinetic data from the ZUMA-5 phase II trial, which forms the basis of the recent approval of axicabtagene ciloleucel.
EXPERT OPINION
Axicabtagene ciloleucel is the first cellular therapy approved for relapsed or refractory follicular lymphoma, demonstrating high rates of durable responses and a manageable toxicity profile in heavily pre-treated patients. | 10.1080/14737140.2022.2096009 |
pubmed_839_23250 | Difficulties in emotional processing have long been regarded as a core difficulty within anorexia nervosa. Recent research and theory have started to highlight how eating disorder symptoms are often used to regulate painful emotions. However, there has been a lack of theoretical sophistication in how emotions have been considered within the eating disorders. This study was designed to use qualitative methodologies to address these inadequacies and provide a richer, more thorough account of emotions within anorexia nervosa. It used a grounded theory methodology to gather and analyse interview data from 11 participants who had a diagnosis of anorexia nervosa, being seen at a regional eating disorder service (both inpatient and day patient). The results highlighted two main overarching themes regarding the perception and management of emotions within anorexia nervosa: (1) development of poor meta-emotional skills; and (2) perception and management of emotion in anorexia nervosa. These two categories comprised of a significant number of components from the qualitative analysis, including difficulties with anger, meta-emotional skills and poverty of emotional environments while growing up. Once the data had been collected and analysed, links were made between the findings of this research and the current literature base. | 10.1002/cpp.631 |
pubmed_845_17728 | Olfactory dysfunction is one of the prodromal symptoms in dementia with Lewy bodies (DLB). However, the molecular pathogenesis associated with decreased smell function remains largely undeciphered. We generated quantitative proteome maps to detect molecular alterations in olfactory bulbs (OB) derived from DLB subjects compared to neurologically intact controls. A total of 3214 olfactory proteins were quantified, and 99 proteins showed significant alterations in DLB cases. Protein interaction networks disrupted in DLB indicated an imbalance in translation and the synaptic vesicle cycle. These alterations were accompanied by alterations in AKT/MAPK/SEK1/p38 MAPK signaling pathways that showed a distinct expression profile across the OB-olfactory tract (OT) axis. Taken together, our data partially reflect the missing links in the biochemical understanding of olfactory dysfunction in DLB. | 10.3390/ijms21176371 |
pubmed_315_2201 | We cloned cholera toxin subunit B gene from 569B and M045 strain of Vibrio cholerae with polymerase chain reaction, constructed recombinant plasmid pCTB, and transformed pCTB into the prokaryotic cell strain JM109. The indentification was made by means of restriction enzyme analysis, polymerase chain reaction, DNA sequencing, SDS-polyacrylamine gel electrophoresis analysis and Western blot. The results indicate that we have amplified cholera toxin subunit B gene of 376 bp from Vibrio cholerae and hve constructed the recombinant plasmid pCTB, and we have affained the object amied at successful expression of 12 KD in the prokaryotic cell strain. | pubmed_315_2201 |
pubmed_329_1818 | We present a review evaluating all litigation claims relating to hip fractures made in a 10-year period between 2005 and 2015. Data was obtained from the NHS Litigation Authority through a freedom of information request. All claims relating to hip fractures were reviewed. During the period analysed, 216 claims were made, of which 148 were successful (69%). The total cost of settling these claims was in excess of £5 million. The introduction of a best-practice tariff by the Department of Health in 2010 was designed to improve the quality of care for hip fracture patients. This was followed by guidance from the National Institute for Health and Clinical Excellence in 2011 and the British Orthopaedic Association in 2012. We analysed claims submitted before and after these guidelines were introduced and no significant difference in the number of claims was noted. The most common cause for litigation was a delay in diagnosis, which accounted for 86 claims in total (40%). Despite the presence of these guidelines and targets, there has not been a significant reduction in the number of claims or an improvement in diagnostic accuracy. This may be due to an increasing level of litigation in the UK but we must also question whether we are indeed providing best-practice care to our hip fracture patients and whether these guidelines need further review. | 10.1308/rcsann.2016.0277 |
pubmed_544_164 | This study demonstrates the presence of an N-acetyl-D-galactosaminyltransferase in human serum and in erythrocyte membranes. This enzyme catalyzes the transfer of N-acetyl-D-galactosamine from UDP-N-acetyl-D-galactosamine to a mucin receptor and 2'-fucosyllactose that have blood group H activity and may be responsible, therefore, for blood group A antigenicity. It was present in the serum of individuals with blood group A or AB but was absent from those with blood group B or O. The activity measured in the erythrocyte membrane was low and did not show clear-cut separation among donors of different blood groups. The specificity of this enzyme in serum was suggested by the ability of 2'-fucosyllactose to act as an acceptor, as well as desialyzed porcine submaxillary mucin, while lactose and desialized fetuin failed to accept N-acetyl-D-galactosamine. The catalytic properties of the N-acetyl-D-galactosaminyltransferase from serum and from erythrocyte membranes were similar. | 10.1073/pnas.68.8.1753 |
pubmed_814_13110 | Negative interspecific mating interactions, known as reproductive interference, can hamper species coexistence in a local patch and promote niche partitioning or geographical segregation of closely related species. Conspecific sperm precedence (CSP), which occurs when females that have mated with both conspecific and heterospecific males preferentially use conspecific sperm for fertilization, might contribute to species coexistence by mitigating the costs of interspecific mating and hybridization. We discussed whether two species exhibiting CSP can coexist in a local environment in the presence of reproductive interference. First, using a behaviorally explicit mathematical model, we demonstrated that two species characterized by negative mating interactions are unlikely to coexist because the costs of reproductive interference, such as loss of mating opportunity with conspecific partners, are inevitably incurred when individuals of both species are present. Second, we experimentally examined differences in mating activity and preference in two Harmonia ladybird species known to exhibit CSP. These behavioral differences may lead to local extinction of H. yedoensis because of reproductive interference by H. axyridis. This prediction is consistent with field observations that H. axyridis uses various food sources and habitats whereas H. yedoensis is confined to a less preferred prey item and a pine tree habitat. Finally, by a comparative approach, we observed that niche partitioning or parapatric distribution, but not sympatric coexistence in the same habitat, is maintained between species with CSP belonging to a wide range of taxa, including vertebrates and invertebrates living in aquatic or terrestrial environments. Taken together, it is possible that reproductive interference may destabilize local coexistence even in closely related species that exhibit CSP. | 10.1002/ece3.7166 |
pubmed_833_9554 | Considering the huge costs and the painful debilitation associated with osteoporosis, some physicians are starting to ask why more attention is not paid to the healthy care and nurturing of good bones in younger women. | pubmed_833_9554 |
pubmed_653_15689 | Road deposited sediments (RDS) are a valuable environmental medium for characterizing contaminant levels in urban areas; and their associated potentially toxic elements (PTEs) can directly impact both human and aquatic health. In this study, RDS were collected from 15 co-located industrial and residential roads throughout Singapore to determine the effect of land use on contaminant levels. A second pilot study was designed to quantify the efficiency of road sweeping in removing different RDS grain size fractions from industrial and residential roads. The fine fraction (<63 μm) of all RDSs was analyzed for over 40 elements. Eleven elements that reflect geogenic and anthropogenic sources were examined in detail (Al, Co, Cr, Cu, Fe, Ni, Pb, Sb, Sc, Si, and Zn). Industrial RDS had statistically higher concentrations of Co, Cr, Fe, and Ni than residential RDS. Potentially toxic elements Cu, Pb, Sb, and Zn were enriched >10-fold at all locations compared to upper continental crust values. Concentrations of Cu, Pb and Zn exceeded aquatic sediment probable effect concentration levels, suggesting they could generate a toxic response in bottom-dwelling aquatic organisms. Traffic was equally heavy at both industrial and residential sites, but large trucks and machinery comprised a larger proportion of the traffic in the industrial areas. Traffic was not significantly correlated with the PTE (i.e., Cu, Pb, Sb and Zn) concentrations. Plausible anthropogenic contaminant sources include vehicles (e.g., brake and tire wear, vehicle emissions) and several industrial activities including metal works, oil processing, and waste incineration. Street sweeping was effective in removal of large organic debris and inorganic RDS, but it was ineffective in removing the geochemically important fraction, i.e., <125 μm. | 10.1016/j.jenvman.2011.11.017 |
pubmed_13_12065 | BACKGROUND
Elevated dynamic plantar pressures are a consistent finding in diabetic patients with peripheral neuropathy, with implications for plantar foot ulceration. This study aimed to investigate whether a first-ray amputation affects plantar pressures and plantar pressure distribution patterns in individuals living with diabetes and peripheral neuropathy.
METHODS
A nonexperimental matched-subject design was conducted. Twenty patients living with diabetes and peripheral neuropathy were recruited. Group 1 (n = 10) had a first-ray amputation and group 2 (n = 10) had an intact foot with no history of ulceration. Plantar foot pressures and pressure-time integrals were measured under the second to fourth metatarsophalangeal joints, fifth metatarsophalangeal joint, and heel using a pressure platform.
RESULTS
Peak plantar pressures under the second to fourth metatarsophalangeal joints were significantly higher in participants with a first-ray amputation ( P = .008). However, differences under the fifth metatarsophalangeal joint ( P = .734) and heel ( P = .273) were nonsignificant. Pressure-time integrals were significantly higher under the second to fourth metatarsophalangeal joints in participants with a first-ray amputation ( P = .016) and in the heel in the control group ( P = .046).
CONCLUSIONS
Plantar pressures and pressure-time integrals seem to be significantly higher in patients with diabetic peripheral neuropathy and a first-ray amputation compared with those with diabetic neuropathy and an intact foot. Routine plantar pressure screening, orthotic prescription, and education should be recommended in patients with a first-ray amputation. | 10.7547/16-021 |
pubmed_415_11247 | Temporal modulation transfer functions (TMTFs) were measured for six users of cochlear implants, using different carrier rates and levels. Unlike most previous studies investigating modulation detection, the experimental design limited potential effects of overall loudness cues. Psychometric functions (percent correct discrimination of modulated from unmodulated stimuli versus modulation depth) were obtained. For each modulation depth, each modulated stimulus was loudness balanced to the unmodulated reference stimulus, and level jitter was applied in the discrimination task. The loudness-balance data showed that the modulated stimuli were louder than the unmodulated reference stimuli with the same average current, thus confirming the need to limit loudness cues when measuring modulation detection. TMTFs measured in this way had a low-pass characteristic, with a cut-off frequency (at comfortably loud levels) similar to that for normal-hearing listeners. A reduction in level caused degradation in modulation detection efficiency and a lower-cut-off frequency (i.e. poorer temporal resolution). An increase in carrier rate also led to a degradation in modulation detection efficiency, but only at lower levels or higher modulation frequencies. When detection thresholds were expressed as a proportion of dynamic range, there was no effect of carrier rate for the lowest modulation frequency (50 Hz) at either level. | 10.1016/j.heares.2011.11.009 |
pubmed_1003_11713 | To explore the venom diversity of Asian pit vipers, we investigated the structure and function of venom phospholipase A2 (PLA2) derived from two primitive tree vipers Trimeresurus puniceus and Trimeresurus borneensis. We purified six novel PLA2s from T. puniceus venom and another three from T. borneensis venom. All cDNAs encoding these PLA2s except one were cloned, and the molecular masses and N-terminal sequences of the purified enzymes closely matched those predicted from the cDNA. Three contain K49 and lack a disulfide bond at C61-C91, in contrast with the D49-containing PLA2s in both venom species. They are less thermally stable than other K49-PLA2s which contain seven disulfide bonds, as indicated by a decrease of 8.8 degrees C in the melting temperature measured by CD spectroscopy. The M110D mutation in one of the K49-PLA2s apparently reduced its edematous potency. A phylogenetic tree based on the amino-acid sequences of 17 K49-PLA2s from Asian pit viper venoms illustrates close relationships among the Trimeresurus species and intergeneric segregations. Basic D49-PLA2s with a unique Gly6 substitution were also purified from both venoms. They showed edema-inducing and anticoagulating activities. It is notable that acidic PLA2s from both venoms inhibited blood coagulation rather than platelet aggregation, and this inhibition was only partially dependent on enzyme activity. These results contribute to our understanding of the evolution of Trimeresurus pit vipers and the structure-function relationships between various subtypes of crotalid venom PLA2. | 10.1111/j.1742-4658.2005.04715.x |
pubmed_78_15301 | Although a vaccine and effective chemotherapy against tuberculosis (TB) have been available for more than half a century, TB was declared a global emergency in 1993. Current chemotherapeutic regimens are being undermined by lack of resources for proper implementation and control, and the emergence of multi-drug resistant strains of Mycobacterium tuberculosis. Several new chemotherapeutic agents are under development, mainly derived from existing anti-TB drugs or broad-spectrum antibiotics. New experimental agents include immunomodulants and drugs directed against novel cellular targets. | 10.1517/13543784.7.4.545 |
pubmed_48_5314 | Primary root (PR) development is a crucial developmental process that is essential for plant survival. The elucidation of the PR transcriptome provides insight into the genetic mechanism controlling PR development in crops. In this study, we performed a comparative transcriptome analysis to investigate the genome-wide gene expression profiles of the seedling PRs of four Brassica napus genotypes that were divided into two groups, short group (D43 and D61), and long group (D69 and D72), according to their extremely different primary root lengths (PRLs). The results generated 55,341,366-64,631,336 clean reads aligned to 62,562 genes (61.9% of the current annotated genes) in the B. napus genome. We provide evidence that at least 44,986 genes are actively expressed in the B. napus PR. The majority of the genes that were expressed during seedling PR development were associated with metabolism, cellular processes, response to stimulus, biological regulation, and signaling. Using a pairwise comparison approach, 509 differentially expressed genes (DEGs; absolute value of log2 fold-change ≥1 and p ≤ 0.05) between the long and short groups were revealed, including phytohormone-related genes, protein kinases and phosphatases, oxygenase, cytochrome P450 proteins, etc. Combining GO functional category, KEGG, and MapMan pathway analyses indicated that the DEGs involved in cell wall metabolism, carbohydrate metabolism, lipid metabolism, secondary metabolism, protein modification and degradation, hormone pathways and signaling pathways were the main causes of the observed PRL differences. We also identified 16 differentially expressed transcription factors (TFs) involved in PR development. Taken together, these transcriptomic datasets may serve as a foundation for the identification of candidate genes and may provide valuable information for understanding the molecular and cellular events related to PR development. | 10.3389/fpls.2016.01238 |
pubmed_754_9678 | Isolated rat aortae were perfused with Krebs buffer in vitro and the synthesis of prostacyclin-like material (PGI2-L) was continuously monitored by measuring the contraction of a superperfused rat stomach strip exposed to the aortic perfusate. PGI2-L release was high after initiation of the aorta perfusion but then gradually declined and stabilized at a basal rate of production that was maintained for at least 180 min. Levels of 6 keto prostaglandin F1 alpha(6ketoPGF1 alpha), the stable breakdown product of PGI2, in the aortic perfusate reflected the changes in biological activity. The concentration of PGE2 in the aortic perfusate remained constant throughout the experiment while the level of thromboxane (Tx)B2 (the stable product of TxA2) decreased with time to below the level of detection of the radioimmunoassay (RIA) used. All biological activity was abolished by heating the aortic perfusate for 30 min at 37 degrees C, while perfusing with 30 microM indomethacin inhibited aorta PGI-L formation. Analysis (by linear regression) of the relationship between PGI2-L formation and the body weight or age of the animals used revealed that PGI2-L synthesis was better related to body weight (r2 = 0.90) than age (r2 = 0.75). | 10.1016/0160-5402(84)90043-3 |
pubmed_168_3277 | A recent study conducted by the Institute of Medicine concluded that there are approximately 1,200 to 1,400 avoidable deaths per year in the U.S. among people living with HIV (PLWH) who do not have health insurance (Institute of Medicine, 2002). The Ryan White Comprehensive AIDS Resources Emergency (CARE) Act was passed by the U.S. Congress in 1990 to provide funding for community-based HIV care services for uninsured and underinsured PLWH--the only Federal program to provide such funding. There is substantial local autonomy in the allocation of CARE Act funds, with planning processes that take place in both States and metropolitan areas. The purpose of this study is to examine trends in the allocation of such funds from 1996 through 2000, the first five years during which effective antiretroviral medications were available for HIV. The study also considers whether these trends were responsive to the evolving modalities of care and the service needs of a changing population of PLWH. | 10.1300/j045v17n04_01 |
pubmed_789_21890 | Genomes of hepatitis E virus (HEV), rubivirus and cutthroat virus (CTV) contain a region of high proline density and low amino acid (aa) complexity, named the polyproline region (PPR). In HEV genotypes 1, 3 and 4, it is the only region within the non-structural open reading frame (ORF1) with positive selection (4-10 codons with dN/dS>1). This region has the highest density of sites with homoplasy values >0.5. Genotypes 3 and 4 show ∼3-fold increase in homoplastic density (HD) in the PPR compared to any other region in ORF1, genotype 1 does not exhibit significant HD (p<0.0001). PPR sequence divergence was found to be 2-fold greater for HEV genotypes 3 and 4 than for genotype 1. The data suggest the PPR plays an important role in host-range adaptation. Although the PPR appears to be hypervariable and homoplastic, it retains as much phylogenetic signal as any other similar sized region in the ORF1, indicating that convergent evolution operates within the major HEV phylogenetic lineages. Analyses of sequence-based secondary structure and the tertiary structure identify PPR as an intrinsically disordered region (IDR), implicating its role in regulation of replication. The identified propensity for the disorder-to-order state transitions indicates the PPR is involved in protein-protein interactions. Furthermore, the PPR of all four HEV genotypes contains seven putative linear binding motifs for ligands involved in the regulation of a wide number of cellular signaling processes. Structure-based analysis of possible molecular functions of these motifs showed the PPR is prone to bind a wide variety of ligands. Collectively, these data suggest a role for the PPR in HEV adaptation. Particularly as an IDR, the PPR likely contributes to fine tuning of viral replication through protein-protein interactions and should be considered as a target for development of novel anti-viral drugs. | 10.1371/journal.pone.0035974 |
pubmed_839_13167 | We conducted an extended follow-up and spatial analysis of the American Cancer Society (ACS) Cancer Prevention Study II (CPS-II) cohort in order to further examine associations between long-term exposure to particulate air pollution and mortality in large U.S. cities. The current study sought to clarify outstanding scientific issues that arose from our earlier HEI-sponsored Reanalysis of the original ACS study data (the Particle Epidemiology Reanalysis Project). Specifically, we examined (1) how ecologic covariates at the community and neighborhood levels might confound and modify the air pollution-mortality association; (2) how spatial autocorrelation and multiple levels of data (e.g., individual and neighborhood) can be taken into account within the random effects Cox model; (3) how using land-use regression to refine measurements of air pollution exposure to the within-city (or intra-urban) scale might affect the size and significance of health effects in the Los Angeles and New York City regions; and (4) what exposure time windows may be most critical to the air pollution-mortality association. The 18 years of follow-up (extended from 7 years in the original study [Pope et al. 1995]) included vital status data for the CPS-II cohort (approximately 1.2 million participants) with multiple cause-of-death codes through December 31, 2000 and more recent exposure data from air pollution monitoring sites for the metropolitan areas. In the Nationwide Analysis, the influence of ecologic covariate data (such as education attainment, housing characteristics, and level of income; data obtained from the 1980 U.S. Census; see Ecologic Covariates sidebar on page 14) on the air pollution-mortality association were examined at the Zip Code area (ZCA) scale, the metropolitan statistical area (MSA) scale, and by the difference between each ZCA value and the MSA value (DIFF). In contrast to previous analyses that did not directly include ecologic covariates at the ZCA scale, risk estimates increased when ecologic covariates were included at all scales. The ecologic covariates exerted their greatest effect on mortality from ischemic heart disease (IHD), which was also the health outcome most strongly related with exposure to PM2.5 (particles 2.5 microm or smaller in aerodynamic diameter), sulfate (SO4(2-)), and sulfur dioxide (SO2), and the only outcome significantly associated with exposure to nitrogen dioxide (NO2). When ecologic covariates were simultaneously included at both the MSA and DIFF levels, the hazard ratio (HR) for mortality from IHD associated with PM2.5 exposure (average concentration for 1999-2000) increased by 7.5% and that associated with SO4(2-) exposure (average concentration for 1990) increased by 12.8%. The two covariates found to exert the greatest confounding influence on the PM2.5-mortality association were the percentage of the population with a grade 12 education and the median household income. Also in the Nationwide Analysis, complex spatial patterns in the CPS-II data were explored with an extended random effects Cox model (see Glossary of Statistical Terms at end of report) that is capable of clustering up to two geographic levels of data. Using this model tended to increase the HR estimate for exposure to air pollution and also to inflate the uncertainty in the estimates. Including ecologic covariates decreased the variance of the results at both the MSA and ZCA scales; the largest decrease was in residual variation based on models in which the MSA and DIFF levels of data were included together, which suggests that partitioning the ecologic covariates into between-MSA and within-MSA values more completely captures the sources of variation in the relationship between air pollution, ecologic covariates, and mortality. Intra-Urban Analyses were conducted for the New York City and Los Angeles regions. The results of the Los Angeles spatial analysis, where we found high exposure contrasts within the Los Angeles region, showed that air pollution-mortality risks were nearly 3 times greater than those reported from earlier analyses. This suggests that chronic health effects associated with intra-urban gradients in exposure to PM2.5 may be even larger between ZCAs within an MSA than the associations between MSAs that have been previously reported. However, in the New York City spatial analysis, where we found very little exposure contrast between ZCAs within the New York region, mortality from all causes, cardiopulmonary disease (CPD), and lung cancer was not elevated. A positive association was seen for PM2.5 exposure and IHD, which provides evidence of a specific association with a cause of death that has high biologic plausibility. These results were robust when analyses controlled (1) the 44 individual-level covariates (from the ACS enrollment questionnaire in 1982; see 44 Individual-Level Covariates sidebar on page 22) and (2) spatial clustering using the random effects Cox model. Effects were mildly lower when unemployment at the ZCA scale was included. To examine whether there is a critical exposure time window that is primarily responsible for the increased mortality associated with ambient air pollution, we constructed individual time-dependent exposure profiles for particulate and gaseous air pollutants (PM2.5 and SO2) for a subset of the ACS CPS-II participants for whom residence histories were available. The relevance of the three exposure time windows we considered was gauged using the magnitude of the relative risk (HR) of mortality as well as the Akaike information criterion (AIC), which measures the goodness of fit of the model to the data. For PM2.5, no one exposure time window stood out as demonstrating the greatest HR; nor was there any clear pattern of a trend in HR going from recent to more distant windows or vice versa. Differences in AIC values among the three exposure time windows were also small. The HRs for mortality associated with exposure to SO2 were highest in the most recent time window (1 to 5 years), although none of these HRs were significantly elevated. Identifying critical exposure time windows remains a challenge that warrants further work with other relevant data sets. This study provides additional support toward developing cost-effective air quality management policies and strategies. The epidemiologic results reported here are consistent with those from other population-based studies, which collectively have strongly supported the hypothesis that long-term exposure to PM2.5 increases mortality in the general population. Future research using the extended Cox-Poisson random effects methods, advanced geostatistical modeling techniques, and newer exposure assessment techniques will provide additional insight. | pubmed_839_13167 |
pubmed_869_2936 | One of the biggest challenges that Mexico faces is to fight against the poverty. The transition of a characteristic welfare model from the government in a closed economy, to an open economy where the functions of the State are limited, has modified the modalities of the social politics against poverty. Six indispensable conditions are identified for poverty's reduction: 1. Economic development with stability in order to generate more and better jobs for poor people. 2. To improve regional economies. 3. To improve home conditions of poor people. 4. To elevate education levels (to encourage an authentic heath education). 5. To diminish catastrophic expenses for health problems. 6. Technical training for all workers. The impact of poverty over health can provide valuable elements to establish effective preventive strategies on health workers. | pubmed_869_2936 |
pubmed_1005_11118 | Alcohol use remains a prominent feature of American collegiate social life. Emerging technological developments, particularly the proliferation of mobile phone cameras and the easy sharing of digital images on social network sites, are now widely integrated into these drinking practices. This paper presents an exploratory study examining how 40 students on a mid-sized college campus in the interior Pacific Northwest incorporate these technologies into their drinking activities. Data from semi-structured interviews are considered within the theoretical framework of 'affordances', which classifies material technologies (camera phones, social network sites) as simultaneously inhabiting the role of artifact shaped by human action and of object that influences human conduct. Our data suggest that although contemporary college drinking reflects longstanding practices, cameras, digital images, and social media introduce new dimensions to college alcohol consumption and memory making processes. These technologies are used to chronicle and archive the festive, social aspects of drinking; commemorate the good times that make up the college experience, and capture proud or incautious displays of excessive drinking. Our examination of emergent college drinking practices seeks to extend understandings of contemporary trends in collegiate alcohol use beyond the discourse of risk and indiscretion to include other important social and cultural dimensions of these phenomena, including pro-social aspects of these practices and the social affordances provided by digital image sharing and reminiscing. | 10.1177/0091450919834970 |
pubmed_314_15410 | BACKGROUND
Hydroa vacciniforme (HV) is a chronic papulovesicular photodermatosis of childhood, with some cases persisting through adulthood. In children, the Epstein-Barr virus (EBV) has been detected in typical HV and in HV evolving into natural killer/T-cell lymphoma. No exploration of EBV infection has been performed in adult patients with HV with long-term follow-up.
OBJECTIVES
To assess EBV infection systematically in blood and in experimentally photoinduced lesions in adult patients with HV.
METHODS
Repeated tests for EBV DNA blood load using real-time polymerase chain reaction (PCR) and serological EBV tests were performed in seven adult patients with long-term follow-up. Skin samples from phototest-induced lesions and surrounding normal skin were studied using PCR, in situ hybridization and electron microscopy. ZEBRA protein was detected using immunostaining. Thirty-five patients with other photosensitive disorders were included as controls.
RESULTS
The EBV DNA blood load was strongly positive in the seven patients with HV and negative in 34 of 35 of the patients with other photosensitive disorders (P < 0.001). The levels were higher in photosensitive patients with HV than in patients with HV in clinical remission. Ultrastructurally, viral particles were detected in lymphocytes and also in keratinocytes in three experimentally phototest-induced lesions; they were not found in the surrounding normal skin. ZEBRA protein was also detected in phototest-induced lesions, but not in the surrounding normal skin.
CONCLUSION
EBV is involved in HV pathogenesis and persists in adult patients with HV. A positive EBV DNA load, specific to HV in the spectrum of photosensitive disorders, might be a useful biomarker in HV. | 10.1111/j.1365-2133.2010.09789.x |
pubmed_919_11324 | BACKGROUND
The present study used the A-line ARX index, derived from auditory evoked potential measurements, to examine the effect of epidural lidocaine on the end-tidal concentration of desflurane during general anesthesia.
METHODS
Thirty ASA I-II patients scheduled for elective colorectal surgery were included and randomized, in a double-blinded fashion, to receive general anesthesia, and 15 ml of either 2% lidocaine (group GE, n=15) or normal saline (group GS, n=15) was administered epidurally with a maintenance infusion rate of 6 ml h-1. After a 10-min high-flow oxygen wash-in period, desflurane was titrated to a target A-line ARX index (AAI) of 20+/-5.
RESULTS
Epidural lidocaine reduced the end-tidal concentration of desflurane required to maintain an adequate clinical effect by 42% compared to general anesthesia alone (2.6% vs. 4.5%, respectively; P<0.001). The initial mean value of AAI was 87.8 (range 78-99) in group GE and 88.13 (79-99) in group GS before general anesthesia induction, the AAI values were approximately 19.7 (15-25) in group GE and 20.2 (16-25) in group GS during anesthesia maintenance, and returned to 84.53 (77-98) in group GE and 86.87 (79-98) in group GS when the patients regained consciousness in the recovery room. No statistical difference in the AAI values was observed either before, during, or after emergence of anesthesia. No patient reported intraoperative awareness.
CONCLUSIONS
Lower-than-expected concentrations of volatile anesthetics are sufficient to maintain appropriate a clinical anesthesia effect during combined general-epidural anesthesia under auditory-evoked potential monitoring. | 10.1111/j.1399-6576.2005.00726.x |
pubmed_328_13230 | BACKGROUND
Pomegranates are healthy fruits rich in bioactive phytochemicals and widely consumed in the human diet. This study was designed to assess their physico-chemical properties and total polyphenolic compounds, along with antioxidant and ascorbic acid concentrations of the skin and juice of seven unstudied pomegranate cultivars grown in Iran.
METHODS
Ten fruits of each of seven selected cultivars were picked. Methanolic extracts from the fruit skins as well as juices were subjected to an evaluation of their physico-chemical properties and phenolic content.
RESULTS
From the pomegranate cultivars studied, the highest juice concentration was measured in ‘Zagh- -e-Zabol’ (72.9 ±2.55%). The highest total soluble solids (18.79 ±1.06 oBrix) of juice, as well as the highest ascorbic acid (16.54 ±2.09 mg/100 g) and total anthocyanin content of skin [11.20 ±2.4 mg CyE (cyanidin- -3-glucoside equivalent)/L] were measured in ‘Bajestan’. Total flavonoids were more concentrated in the skin of ‘Siah-e-Zabol’ [930 ±16 mg QuE (quercetin equivalent)/L]. In the juice of ‘Rabab-e-Pust Ghermez’ and ‘Malas-e-Saveh’ the highest concentrations of phenolic compounds were recorded [1082 ±12.8 mg GaE (gal- lic acid equivalent)/L] and tannins [6.55 ±0.5 mg TaE (tannic acid equivalent)/L], respectively.
CONCLUSIONS
Significant differences were assessed between the skin and juice of the cultivars in terms of their physico-chemical properties and polyphenolic contents. The results showed higher levels of total tannins, phenolics and antioxidant activity in juice of pomegranate, whereas the skins possessed higher total flavo- noid, anthocyanin and ascorbic acid content. Further phytochemical analysis are therefore needed to identify the most representative phenylpropanoids by LC-MS (liquid chromatography coupled to mass spectrometry) and to develop novel and promising dietary supplements. | 10.17306/J.AFS.0584 |
pubmed_1090_11187 | Five patients representing different categories of glossal resection were fitted with prostheses specifically designed to improve speech. Speech recordings made for subjects with and without their prostheses were subjected to a variety of analyses. Prosthetic influence on listeners' judgments of severity level/intelligibility, number of consonants in error, and on the acoustic measure F2 range of vowels was evaluated. Findings indicated that all subjects demonstrated improvement on the speech measures. However, the extent of improvement on each measure varied across speakers and resection categories. Implications of the findings for prosthetic speech rehabilitation in this population are discussed. | 10.1016/0022-3913(90)90301-r |
pubmed_1107_5531 | Tissue eosinophilia was observed in the subcutaneous tissue of mice shortly after their inoculation not only with living but also with lysed promastigotes of Leishmania amazonensis. Intraperitoneal inoculation of lysed promastigotes from five different Leishmania species (L. donovani, L. chagasi, L. tropica, L. amazonensis, and L. braziliensis) induced eosinophil accumulation in the mouse peritoneum. This eosinophil infiltration was also detected in C5-deficient AKR mice, indicating complement independent eosinophil chemotaxis by the parasite. The induced eosinophils were hypodense, suggesting activation of the cells. Finally, we demonstrated in vitro eosinophil chemotactic activity in the promastigote lysates using purified eosinophils and blind well chambers. These results suggest the presence of an eosinophil chemotactic factor in Leishmania, a protozoan parasite. | 10.1007/s004360050150 |
pubmed_21_21046 | PURPOSE
To describe a modified glaucoma staging system (Modified GSS) based on the visual field index (VFI) and evaluate the performance of the Modified GSS compared with the Bascom Palmer GSS and Enhanced GSS.
METHODS
A total of 549 eyes of 549 patients were studied retrospectively. The Modified GSS was used to classify the glaucomatous visual field defects into stage 0 to 5 based on the VFI. The cutoff values for each stage were derived from VFI that were equivalent to mean deviations of -6, -12, -20, and -25 dB by receiver operating characteristic analysis. The staging performances, based on each of three GSSs, were compared with both the Advanced Glaucoma Intervention Study (AGIS) and Collaborative Initial Glaucoma Treatment Study (CIGTS) scores.
RESULTS
The VFI cutoff values calculated for each stage were 81.5, 62.5, 42.5, and 22.5%, respectively. The correlation coefficient of Modified GSS was greater than that of Bascom Palmer GSS (p < 0.001), and correlation coefficients of Modified GSS and Enhanced GSS were equivalent. However, Enhanced GSS tended to classify moderate to severe AGIS and CIGTS scores into higher stages (p < 0.001).
CONCLUSIONS
The Modified GSS is easy to use and accurate, and the staging performance is either equal or superior to existing GSSs. | 10.1007/s00417-013-2490-5 |
pubmed_483_15225 | OBJECTIVE
Longitudinal research supports an effect of participation in aspects of community life (e.g., leisure activity, employment) on neurocognition in the general population. This study examined the extent and nature of the relationship between community participation and neurocognition among people with serious mental illnesses.
METHOD
Participants included 168 adults with schizophrenia spectrum or affective disorder diagnoses who completed the Temple University Community Participation Measure and Brief Assessment of Cognition in Schizophrenia. Hierarchical multiple regression analyses explored linear and curvilinear effects of the amount and breadth of community participation on neurocognition.
RESULTS
Significant linear relationships existed between amount of community participation and overall neurocognitive functioning, motor speed, verbal fluency, and attention/processing speed, and between breadth of participation and verbal fluency. Significant curvilinear effects were noted between amount of community participation and verbal memory, and between breadth of community participation and overall neurocognitive functioning and motor speed.
CONCLUSIONS AND IMPLICATIONS FOR PRACTICE
Findings suggest that enhanced community participation may contribute to improved neurocognitive functioning, further supporting the importance of this rehabilitation target. (PsycINFO Database Record (c) 2019 APA, all rights reserved). | 10.1037/prj0000364 |
pubmed_510_7680 | Left ventricular stroke distance was measured by Doppler ultrasound in 10 doxorubicin-treated and 10 control patients. Measurements were made 10 min, 2 h and 4 h after drug administration. Stroke distance (a linear analogue of stroke volume) increased significantly from 12.6 cm (S.D. 2.7) before and 12.5 cm (S.D. 2.7) 10 min after, to 13.6 cm (S.D. 2.8) 2 h after and 13.7 cm (S.D. 2.7) 4 h after doxorubicin (p less than 0.05). Throughout the study period there were no significant changes in stroke distance in the control patients who were infused with similar fluid volumes, and no significant changes in heart rate or blood pressure in either group. These observations confirm previous findings made by radionuclide ventriculography, a much more complex, expensive and hazardous technique, not amenable to repetition at short time intervals. The measurement of stroke distance by Doppler ultrasound is a convenient bedside method of assessing acute hemodynamic changes after doxorubicin or any drug affecting cardiac function. The method we describe is eminently suitable for investigating the cardiotoxicity of chemotherapeutic agents. | 10.1002/hon.2900090107 |
pubmed_708_6558 | The new cloned serotype 2 Marek's disease viruses (MDV) of ML-6, ML-9, and ML-22 strains were inoculated in specific-pathogen-free (SPF) chicks to evaluate the pathogenicity and protective efficacy. Chicks inoculated or contact-infected with ML strains showed no gross and histological lesions in lymphoid organs, sciatic plexuses and other visceral organs during 10 weeks of observation periods, indicating that the viruses were non-pathogenic. Moreover, the viruses were found to be spread horizontally among chicks by demonstrating the presence of viremia in contacted chicks at 2 weeks-old. Chicks vaccinated with ML-6 at one day-old were protected against subsequent challenge by inoculation with virulent MDV strain of Md/5 at 4 or 7 days old or by contact infection at 7 days old with chickens previously inoculated with the same strain. | 10.1292/jvms1939.52.329 |
pubmed_332_8963 | The (pro)renin receptor (PRR) was initially believed to be a contributor to the pathogenesis of cardiovascular diseases via the amplification of renin- or prorenin-induced angiotensin (Ang) formation. However, a recent paradigm shift suggests a new role for PRR, separate from the renin-angiotensin system (RAS), in contributing to cellular homeostasis. Specifically, PRR is thought to be essential for vacuolar H(+) -ATPase (V-ATPase) activity and acts as an adaptor between the V-ATPase and the Wnt signalling pathway. Recent PRR conditional knock-out studies have confirmed this link between V-ATPase and PRR, with deletion resulting in the accumulation of autophagic vacuoles and animal lethality. The molecular mechanism by which PRR contributes to V-ATPase activity, and whether multiple signalling pathways are affected by PRR loss, is currently unknown. Additionally, cleavage by furin at a single site within full-length PRR results in the production of a soluble form of the receptor, which is detectable in plasma. Soluble PRR is hypothesized to bind to specific ligands and receptors and mediate signal transduction pathways. Understanding the physiological function of full-length and soluble PRR will be important for establishing its role in pathology. | 10.3109/07853890.2012.660496 |
pubmed_437_1428 | BACKGROUND
Twins, compared to singletons, have an increased risk of perinatal mortality and morbidity, due mainly to a higher prevalence of preterm birth and low birthweight. Intrauterine growth restriction (IUGR) is also common and can affect one or both fetuses. In some cases, however, one twin is much smaller than the other (growth discordance). Usually, high birthweight discordance is associated with increased perinatal morbidity. The aim of this study is to describe the epidemiological features of a population of twins at birth, with particular reference to the interpretation and clinical effects of birthweight discordance.
METHODS
We evaluated retrospectively the clinical features of 70 infants born from twin pregnancies and assessed birthweight discordance in 31 pregnancies where both twins were followed at our institution. Discordance was treated both as a continuous and a categorical variable, using a cutoff of 18%. Possible relationships between birthweight discordance and other variables, such as maternal age, gestational age, birthweight percentile, number of SGA newborns in the pair, Hematocrit (Ht) discordance and neonatal anemia, prevalence of malformations, neonatal morbidity and death, were analyzed.
RESULTS
In our cohort birthweight percentile decreased slightly with increasing gestational age. Birthweight discordance, on the contrary, increased slightly with the increase of gestational age.A high discordance is associated to the presence of one SGA twin, with the other AGA or LGA. In our population, all 6 pregnancies in which discordance exceeded 18% belonged to this category (one SGA twin).Ht discordance at birth is associated to the presence of neonatal anemia in a twin, but it is not significantly related to weight discordance.Finally, in our case history, weight discordance is not associated in any way with the prevalence of malformations, morbidity and mortality.
CONCLUSIONS
Birthweight discordance is an important indicator of complications that act asymmetrically on the two fetuses, affecting intrauterine growth in one of them, and usually determining the birth of a SGA infant.Our case history shows a significant statistical association between pair discordance and IUGR in one of the twins, but we could not demonstrate any relationship between discordance and the prevalence of malformations, morbidity and mortality. | 10.1186/1824-7288-40-43 |
pubmed_341_12576 | Purpose
To identify the genetic basis for retinitis pigmentosa (RP) in a cohort of Jewish patients from Caucasia.
Methods
Patients underwent a detailed ophthalmic evaluation, including funduscopic examination, visual field testing, optical coherence tomography (OCT), and electrophysiological tests, electroretinography (ERG) and visual evoked potentials (VEP). Genetic analysis was performed with a combination of whole exome sequencing (WES) and Sanger sequencing. Bioinformatic analysis of the WES results was performed via a customized pipeline. Pathogenicity of the identified intronic variant was evaluated in silico using the web tool Human Splicing Finder, and in vitro, using a minigene-based splicing assay. Linkage disequilibrium (LD) analysis was used to demonstrate a founder effect, and the decay of LD over generations around the mutation in Caucasus Jewish chromosomes was modeled to estimate the age of the most recent common ancestor.
Results
In eight patients with RP from six unrelated families, all of Caucasus Jewish ancestry, we identified a novel homozygous intronic variant, located at position -9 of PDE6B intron 15. The c.1921-9C>G variant was predicted to generate a novel acceptor splice site, nine bases upstream of the original splice site of intron 15. In vitro splicing assay demonstrated that this novel acceptor splice site is used instead of the wild-type site, leading to an 8-bp insertion into exon 16, which is predicted to cause a frameshift. The presence of a common ancestral haplotype in mutation-bearing chromosomes was compatible with a founder effect.
Conclusions
The PDE6B c.1921-9C>G intronic mutation is a founder mutation that accounts for at least 40% (6/15 families) of autosomal recessive RP among Caucasus Jews. This result is highly important for molecular diagnosis, carrier screening, and genetic counseling in this population. | pubmed_341_12576 |
pubmed_416_20576 | The Yant Award was established in 1964 to honor the contributions of William P. Yant, the first president of the American Industrial Hygiene Association. It is presented annually for outstanding contributions in industrial hygiene or allied fields to an individual residing outside the United States. | 10.1080/15459620600923261 |
pubmed_223_5186 | Allele-specific RNA silencing has been shown to be an effective therapeutic treatment in a number of diseases, including neurodegenerative disorders. Studies of allele-specific silencing in hypertrophic cardiomyopathy (HCM) to date have focused on mouse models of disease. We here examine allele-specific silencing in a human-cell model of HCM. We investigate two methods of silencing, short hairpin RNA (shRNA) and antisense oligonucleotide (ASO) silencing, using a human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model. We used cellular micropatterning devices with traction force microscopy and automated video analysis to examine each strategy's effects on contractile defects underlying disease. We find that shRNA silencing ameliorates contractile phenotypes of disease, reducing disease-associated increases in cardiomyocyte velocity, force, and power. We find that ASO silencing, while better able to target and knockdown a specific disease-associated allele, showed more modest improvements in contractile phenotypes. These findings are the first exploration of allele-specific silencing in a human HCM model and provide a foundation for further exploration of silencing as a therapeutic treatment for MYH7-mutation-associated cardiomyopathy. | 10.1152/physiolgenomics.00021.2020 |
pubmed_733_20355 | BACKGROUND
Therapeutic options to treat atopic dermatitis are limited. Leukocytes from atopic patients have an abnormally high activity of cyclic adenosine monophosphate (AMP)-phosphodiesterase (PDE), which can be normalized in vitro by PDE inhibitors. Cipamfylline is a new potent and selective inhibitor of PDE-4.
OBJECTIVES
To compare the efficacy and safety of up to 14 days' topical treatment with cipamfylline (0.15%) cream with vehicle and with hydrocortisone 17-butyrate (0.1%) cream.
PATIENTS AND METHODS
International, multicentre, prospective, randomized double-blind, left-right studies of cipamfylline vs. vehicle and cipamfylline vs. hydrocortisone 17-butyrate in adult patients with stable symmetrical atopic dermatitis on the arms.
RESULTS
Both cipamfylline and hydrocortisone 17-butyrate reduced the Total Severity Score significantly (P < 0.001). The reduction with cipamfylline was significantly greater than that with vehicle (difference vehicle-cipamfylline 1.67 95% confidence interval (CI) 1.06, 2.28; P < 0.001) and was significantly less than with hydrocortisone 17-butyrate (difference hydrocortisone-cipamfylline -2.10 95% CI -2.93, -1.27; P < 0.001). Investigator and patient assessments of the overall treatment response showed a similar picture.
CONCLUSIONS
Cipamfylline cream is significantly more effective than vehicle, but significantly less effective than hydrocortisone 17-butyrate cream in the treatment of atopic dermatitis. | 10.1046/j.1365-2133.2002.04894.x |
pubmed_899_8314 | The introduction of agents such as thalidomide, lenalidomide, and bortezomib has changed the management of patients with multiple myeloma who are not eligible for autologous transplantation, many of whom are elderly. We sought to compare three thalidomide-based oral regimens among such patients in Latin America. We randomized patients with newly diagnosed multiple myeloma with measurable disease to one of the following regimens: melphalan, prednisone, and thalidomide (MPT); cyclophosphamide, thalidomide, and dexamethasone (CTD); and thalidomide and dexamethasone (TD). The TD arm was closed prematurely and was analyzed only descriptively. The primary endpoint was the overall response rate (ORR), whereas progression-free survival (PFS) and overall survival (OS) were secondary endpoints. The accrual rate was slower than expected, and the study was terminated after 82 patients had been randomized. The ORRs were 67.9 % with MPT, 89.7 % with CTD, and 68.7 % with TD (p = 0.056 for the comparison between MPT and CTD). The median PFS was 24.1 months for MPT, 25.9 months for CTD, and 21.5 months for TD. There were no statistically significant differences in PFS or OS between MPT and CTD. In an unplanned logistic regression analysis, ORR was significantly associated with treatment with CTD (p = 0.046) and with performance status of 0 or 1 (p = 0.035). Based on the current results, no definitive recommendations can be made regarding the comparative merit of the regimens tested. Nevertheless and until the results of further studies become available, we recommend either CTD or MPT as suitable frontline regimens for patients with multiple myeloma who are not candidates to transplantation in settings where lenalidomide and bortezomib are not available. | 10.1007/s00277-015-2537-2 |
pubmed_163_26176 | The Pyraloidea is one of the species-rich superfamilies of Lepidoptera and contains numerous economically important pest species that cause great loss in crop production. Here, we sequenced and annotated nine complete mitogenomes for Pyraloidea, and further performed various phylogenetic analyses, to improve our understanding of mitogenomic evolution and phylogeny of this superfamily. The nine mitogenomes were circular, double-stranded molecules, with the lengths ranging from 15,214 bp to 15,422 bp, which are comparable to other reported pyraloid mitogenomes in size. Gene content and arrangement were highly conserved and are typical of Lepidoptera. Based on the hitherto most extensive mitogenomic sampling, our various resulting trees showed generally congruent topologies among pyraloid subfamilies, which are almost in accordance with previous multilocus studies, indicating the suitability of mitogenomes in inferring high-level relationships of Pyraloidea. However, nodes linking subfamilies in the "non-PS clade" were not completely resolved in terms of unstable topologies or low supports, and future investigations are needed with increased taxon sampling and molecular data. Unexpectedly, Orybina Snellen, represented in a molecular phylogenetic investigation for the first time, was robustly placed as basal to the remaining Pyralidae taxa across our analyses, rather than nested in Pyralinae of Pyralidae as morphologically defined. This novel finding highlights the need to reevaluate Orybina monophyly and its phylogenetic position by incorporating additional molecular and morphological evidence. | 10.3390/insects12111039 |
pubmed_615_19422 | BACKGROUND
Uncorrected developmental dysplasia of the hip (DDH) is associated with long-term morbidity such as gait abnormalities, chronic pain and degenerative arthritis.
OBJECTIVES
To determine the effect of different screening programmes for DDH on the incidence of late presentation of congenital hip dislocation.
SEARCH METHODS
Searches were performed in CENTRAL (The Cochrane Library), MEDLINE and EMBASE (January 2011) supplemented by searches of clinical trial registries, conference proceedings, cross references and contacting expert informants.
SELECTION CRITERIA
Randomised, quasi-randomised or cluster trials comparing the effectiveness of screening programmes for DDH.
DATA COLLECTION AND ANALYSIS
Three independent review authors assessed study eligibility and quality, and extracted data.
MAIN RESULTS
No study examined the effect of screening (clinical and/or ultrasound) and early treatment versus not screening and later treatment. One study reported universal ultrasound compared to clinical examination alone did not result in a significant reduction in late diagnosed DDH or surgery but was associated with a significant increase in treatment. One study reported targeted ultrasound compared to clinical examination alone did not result in a significant reduction in late diagnosed DDH or surgery, with no significant difference in rate of treatment. Meta-analysis of two studies found universal ultrasound compared to targeted ultrasound did not result in a significant reduction in late diagnosed DDH or surgery. There was heterogeneity between studies reporting the effect on treatment rate. Meta-analysis of two studies found delayed ultrasound and targeted splinting compared to immediate splinting of infants with unstable (but not dislocated) hips resulted in no significant difference in the rate of late diagnosed DDH. Both studies reported a significant reduction in treatment with use of delayed ultrasound and targeted splinting. One study reported delayed ultrasound and targeted splinting compared to immediate splinting of infants with mild hip dysplasia on ultrasound resulted in no significant difference in late diagnosed DDH but a significant reduction in treatment. No infants in either group received surgery.
AUTHORS' CONCLUSIONS
There is insufficient evidence to give clear recommendations for practice. There is inconsistent evidence that universal ultrasound results in a significant increase in treatment compared to the use of targeted ultrasound or clinical examination alone. Neither of the ultrasound strategies have been demonstrated to improve clinical outcomes including late diagnosed DDH and surgery. The studies are substantially underpowered to detect significant differences in the uncommon event of late detected DDH or surgery. For infants with unstable hips or mildly dysplastic hips, use of delayed ultrasound and targeted splinting reduces treatment without significantly increasing the rate of late diagnosed DDH or surgery.
PLAIN LANGUAGE SUMMARY
Screening methods for dislocated or improperly formed hips in newborn infants The hip joint is a ball and socket joint. Newborns may have hips that are not in their socket (dislocated) or hips that are improperly formed (dysplasia). Risk factors for hip dysplasia include a family history of a similar problem and female infants delivered in the breech position. The hips of most newborns will be examined clinically after birth and during infancy to determine whether they are stable, unstable or dislocated. Screening for hip dysplasia may prevent the need for late treatment, which is associated with long term hip deformity, gait disturbance and arthritis. However, early screening leads to increased treatment. Treatment may be complicated by damage to the hip due to impairment of the blood supply (avascular necrosis). This review found no studies that compared the benefits and costs of early screening versus not screening for hip problems. Studies that compared the addition of ultrasound to clinical examination reported that when ultrasound was performed on all infants, the rate of treatment increased with no significant difference in rate of late detected dysplasia or surgery. Targeted ultrasound to infants at high risk of hip dysplasia did not significantly increase the rate of treatment but also did not significantly reduce the rate of late detected dysplasia or surgery. It is not possible to give clear recommendations for hip screening of newborn infants from the available evidence. Where infants are clinically detected as having unstable but not dislocated hips, or are detected on ultrasound to have mild hip dysplasia, there is evidence that delaying treatment by two to eight weeks reduces the need for treatment without a significant increase in late diagnosed dysplasia or surgery. | 10.1002/ebch.1891 |
pubmed_1118_11582 | PURPOSE
New generation of receptor tyrosine kinase inhibitors (RTKIs) have shown to improve survival in many solid tumors. However, an imaging biomarker is needed for patient selection and prediction of treatment response. This study evaluates the use of quantitative changes of HER3 on 68 Ga-NOTA-HER3P1 PET/MRI for prediction of early response to pan-RTKIs in gastric cancer (GCa).
PROCEDURES
GCa cell lines were evaluated for expression of RTKs, and downstream signaling pathways (AKT and MAPK). Cell viability was assessed following 24-72 h of treatment with 0.01-1 µmol/L of afatinib, a pan-RTKI. HER3-expressing afatinib-sensitive (NCI-N87) and resistant cells (SNU16) were selected for evaluation of changes in RTKs expression and downstream pathways, with 24-72 h of 0.1 µmol/L afatinib treatment. 68 Ga-NOTA-HER3P1 PET/MRI was performed in subcutaneous NCI-N87 and SNU16 xenografts (nu:nu, n = 12/group) at baseline and 4 days after afatinib treatment (10 mg/kg, PO, daily). Temporal changes in PET measures were correlated to HER3 expression in tumors, tumor growth rate, and treatment response.
RESULTS
With afatinib therapy, NCI-N87 cells showed increased total HER3 expression, and reduction of other RTKs and downstream nodes within 72 h, while SNU16 cells showed no significant change in total HER3 and downstream nodes. 68 Ga-HER3P1 PET/MRI showed increased uptake in NCI-N87 and no significant change in SNU16 tumors (day 4 vs. baseline SUVmean: 3.8 ± 0.7 vs. 1.6 ± 0.6, p < 0.05 in NCI-N87, and 1.5 ± 0.7 vs. 1.7 ± 0.7, p > 0.05 in SNU16). These findings were in concordance with HER3 expression in histopathological analyses and tumor growth over 3 weeks of treatment (mean tumor volume in treated vs. control: 11 ± 17 mm3 vs. 293 ± 79 mm3, p < 0.001 in NCI-N87, and 238 ± 91 mm3 vs. 282 ± 35 mm3, p > 0.05 in SNU16).
CONCLUSIONS
Quantitative changes in HER3 PET could be used to predict response to pan-RTKI within few days after initiation of treatment and can help with personalizing GCa management. | 10.1007/s11307-022-01763-9 |
pubmed_298_12174 | The main aim of our study was analysis of adsorption dynamics of mixtures containing quaternary derivatives of lysosomotropic substance (QDLS). Two types of equimolar mixtures were considered: the ones containing two derivatives of lysosomotropic substances (DMALM-12 and DMGM-12) as well as the catanionic mixtures i.e. the systems containing QDLS and DBSNa. Dynamic surface tension measurements of surfactant mixtures were made. The results suggested that the diffusivity of the mixed system could be treated as the average value of rates of diffusion of individual components, micelles and ion pairs, which are present in the mixtures studied. Moreover, an attempt was made to explain the influence of the presence of micelles in the mixtures on their adsorption dynamics. The compounds examined show interesting biological properties which can be useful, especially for drug delivery in medical treatment. In vitro cytotoxic activities of the mixtures studied towards human cancer cells were evaluated. Most of the mixtures showed a high antiproliferative potential, especially the ones containing DMALM-12. Each cancer cell line used demonstrated different sensitivity to the same dose of the mixtures tested. | pubmed_298_12174 |
pubmed_460_3924 | Ion-trap LC/MS/MS was evaluated for use in the determination of acrylamide (AA) in processed foods. Multiple reaction monitoring (MRM) analysis of a series of AA standard solutions containing deuterium-labeled acrylamide (AA-d3) as an internal standard was performed. A linear relationship between the concentration of AA and the ratio of peak area (AA/AA-d3) in the extracted ion chromatogram (m/z 55, 58 derived from m/z 72, 75, respectively) was obtained over a wide range of 2-20,000 ng/mL. The quantification limit of AA was 2 ng/mL. In analyses of 37 commercial foods, AA was detected in a potato snack at the maximum value of 3,570 ng/g and found in 23 foods prepared or cooked at high temperature. The samples were analyzed in triplicate and the relative standard deviations (RSD) were less than 15% in many processed foods. | 10.3358/shokueishi.45.95 |
pubmed_965_7132 | A sensitive method for the spectrophotometric determination of ruthenium with the ferroinyielding as-triazines has been developed. This method has several advantages; complete reduction of ruthenium species to ruthenium(II) can be achieved by the recommended procedure, which shortens the colour development time, saves the unnecessary use of several-fold excess of the reagent and the molar absorptivity is increased significantly. A few of the new as-triazines together with the commercially available Ferene(R) have been evaluated as ruthenium(II) chromogens. 3-(2-Pyridyl)-5,6-diphenyl-as-triazine (PDT) and ferrozine, a sulphonated derivative of PDT, have been re-evaluated by the new method. It has been observed that the as-triazine acting as a bidentate ligand forms a tris-complex with ruthenium(II) similar to its reaction with iron(II). | 10.1016/0039-9140(92)80122-t |
pubmed_1134_16668 | In both yeast and mammals, uncapped telomeres activate the DNA damage response (DDR) and undergo end-to-end fusion. Previous work has shown that the Drosophila HOAP protein, encoded by the caravaggio (cav) gene, is required to prevent telomeric fusions. Here we show that HOAP-depleted telomeres activate both the DDR and the spindle assembly checkpoint (SAC). The cell cycle arrest elicited by the DDR was alleviated by mutations in mei-41 (encoding ATR), mus304 (ATRIP), grp (Chk1) and rad50 but not by mutations in tefu (ATM). The SAC was partially overridden by mutations in zw10 (also known as mit(1)15) and bubR1, and also by mutations in mei-41, mus304, rad50, grp and tefu. As expected from SAC activation, the SAC proteins Zw10, Zwilch, BubR1 and Cenp-meta (Cenp-E) accumulated at the kinetochores of cav mutant cells. Notably, BubR1 also accumulated at cav mutant telomeres in a mei-41-, mus304-, rad50-, grp- and tefu-dependent manner. Our results collectively suggest that recruitment of BubR1 by dysfunctional telomeres inhibits Cdc20-APC function, preventing the metaphase-to-anaphase transition. | 10.1038/ng.2007.64 |
pubmed_213_3105 | The Authors report their experience concerning 256 cases of Raynaud's Disease and Syndrome observed from 1968 to 1987; 23 patients underwent surgery for the treatment of dystrophic or gangrenous lesions of the extremities (12 cervico-thoracic and 8 lumbar sympathectomies, 1 popliteal aneurysmectomy, 2 scalenotomies): a significant improvement of the clinical picture was observed in 91.30% of the patients who underwent the operation. The pharmacologic treatment obtained satisfactory results in 51.26% of all the patients. The Authors propose a three stage classification of raynaudian symptoms: I stage: sporadic vasoconstrictive crises; II stage: recurrent vasoconstrictive crises not invalidating working activity and "restitutio ad integrum" between attacks; III stage: recurrent and frequent crises invalidating working activity with asphyxia and/or ulcer-gangrene of the extremities. Both pharmacological and surgical treatment obtained the improvement of the clinical condition to an inferior stage in a high rate of patients. In three patients only (two of whom underwent scalenotomy and one popliteal aneurysmectomy) the complete and definitive cessation of raynaudian crises was observed. | pubmed_213_3105 |
pubmed_524_11391 | Bivalve molluscs have the potential to bioaccumulate microbial pathogens including noroviruses from aquatic environments and as such, there is a need for a rapid and cheap in-situ method for their detection. Here, we characterise the tissue-specific response of New Zealand Greenshell™ mussels (Perna canaliculus) to faecal contamination from two different sources (municipal sewage and human faeces). This is done with the view to identify potential biomarkers that could be further developed into low cost, rapid and sensitive in-situ biosensors for human faecal contamination detection of mussels in growing areas. Tissue-specific metabolic profiles from gills, haemolymph and digestive glands were analysed using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). Clear differentiation of metabolic profiles was observed among treatments in each tissue type. Overall, energy pathways such as glycolysis, citrate cycle and oxidative phosphorylation were downregulated across the three mussel tissues studied following simulated contamination events. Conversely, considerable sterol upregulation in the gills was observed after exposure to contamination. Additionally, free pools of nucleotide phosphates and the antioxidant glutathione declined considerably post-exposure to contamination in gills. These results provide important insights into the tissue-specific metabolic effects of human faecal contamination in mussels. This study demonstrates the utility of metabolomics as a tool for identifying potential biomarkers in mussels. | 10.1016/j.scitotenv.2021.145363 |
pubmed_476_3184 | Background: To evaluate how an international one-year intensive research training program for addiction medicine physicians contributed to subsequent research involvement and productivity. Methods: We prospectively compared addiction medicine physician fellows admitted to a one-year training program with non-admitted controls, using baseline questionnaire and peer-reviewed publication data. Participants' publication activity was assessed from fellowship application date onwards using biomedical databases (e.g., PubMed, Embase). Results: Between July 2014 and June 2020, which is six years of cohorts, 56 (39 women) physicians, both fellows (n = 25) and non-admitted applicants (n = 31), were observed and included in the study, contributing 261 person-years of observation. At baseline, in the fellows' cohort: 76% of participants (19/25) reported past research involvement, 24% (6/25) had one or more advanced graduate degrees (e.g., MPH), and the median number of peer-reviewed, first author publications was one (Interquartile Range [IQR] = 0-2). At baseline, in the controls' cohort: 84% of participants (26/31) reported past research involvement, 39% (12/31) had one or more advanced graduate degrees, and the median number of peer-reviewed, first author publications was zero. The physicians' training included internal medicine (n = 8), family medicine (n = 33), psychiatry (n = 5) and others (n = 4). At follow up, there was a significant difference between fellows (n = 25) and controls (n = 31) in total number of publications (Rate Ratio [RR] = 13.09, 95% Confidence Interval [CI], 5.01 - 34.21, p < 0.001), as well as first author publications (RR = 5.59, 95% CI, 2.23 - 14.06, p < 0.001). Conclusion: In the six-year observation period, fellows' productivity indicates undertaking this fellowship was associated with significant research outputs in comparison to controls, signaling successful training of addiction physicians to help recruit addiction medicine physicians to participate in addiction research. | 10.1080/08897077.2021.2010256 |
pubmed_1065_19386 | Several lines of evidence have postulated that reduction in the activity of lipoprotein lipase (LPL) is involved in cachexia induction in cancer patients. Recently we have demonstrated that murine melanoma B16 has the ability to reduce the LPL activity and thereby induce cachexia symptoms in mice following intraperitoneal inoculation. In order to further investigate the relationship between LPL activity and cachectic syndrome, cachexia models other than melanoma B16 are required. However, there are few animal cachexia models in which LPL activity is involved in the induction of cachectic symptoms. In this study, cachectic symptoms and plasma LPL activity were investigated in mice bearing EL-4 mouse lymphoma. In EL-4 bearing mice the body weight including tumor weight in the abdominal cavity was rather higher than that of normal mice without tumor, whereas weights of carcass wet and gastrocnemius muscle were significantly decreased in EL-4 bearing mice. Elevated blood levels of triglyceride and non-esterified fatty acid were observed in mice bearing EL-4, associated with the impaired plasma LPL activity. Overall, this study indicated that EL-4 lymphoma in mice results in a severe cachexia which is possibly related to impaired LPL activity and also provided a useful cachexia model for understanding the role of LPL in the development of cancer cachexia. | pubmed_1065_19386 |
pubmed_1122_662 | Much attention has focused on the important role played by phosphatases in the control of gene transcription, cell differentiation and memory regulation. It is also clear that phosphatases may regulate a number of biochemical pathways which can modulate cellular function. Of particular interest is the role of phosphatases in the control of neuronal function. Alterations in neuronal function may contributed to the heightened airways responsiveness observed in asthma to a number of physiological stimuli including distilled water, sulfur dioxide, metabisulfite, hypertonic saline, exercise, allergens, viruses and cold air. An understanding of the mechanisms which regulate the function of sensory nerves could have important clinical implications. In this review we will highlight a number of studies that have investigated the role of phosphatases in the regulation of airway nerve function. | 10.1016/s0306-3623(98)00204-3 |
pubmed_984_9555 | Climbing fiber input produces complex spike synchrony across populations of cerebellar Purkinje cells oriented in the parasagittal axis. Elucidating the fine spatial structure of this synchrony is crucial for understanding its role in the encoding and processing of sensory information within the olivocerebellar cortical circuit. We investigated these issues using in vivo multineuron two-photon calcium imaging in combination with information theoretic analysis. Spontaneous dendritic calcium transients linked to climbing fiber input were observed in multiple neighboring Purkinje cells. Spontaneous synchrony of calcium transients between individual Purkinje cells falls off over approximately 200 microm mediolaterally, consistent with the presence of cerebellar microzones organized by climbing fiber input. Synchrony was increased after administration of harmaline, consistent with an olivary origin. Periodic sensory stimulation also resulted in a transient increase of synchrony after stimulus onset. To examine how synchrony affects the neural population code provided by the spatial pattern of complex spikes, we analyzed its information content. We found that spatial patterns of calcium events from small ensembles of cells provided substantially more stimulus information (59% more for seven-cell ensembles) than available by counting events across the pool without taking into account spatial origin. Information theoretic analysis indicated that, rather than contributing significantly to sensory coding via stimulus dependence, correlational effects on sensory coding are dominated by redundancy attributable to the prevalent spontaneous synchrony. The olivocerebellar circuit thus uses a labeled line code to report sensory signals, leaving open a role for synchrony in flexible selection of signals for output to deep cerebellar nuclei. | 10.1523/JNEUROSCI.4919-08.2009 |
pubmed_1031_16689 | PURPOSE
The development of a practical, real-time dosimetry system should result in improved implant dose distributions and higher prostate cancer control rates. Our purpose here is to demonstrate that intraoperative isodose reconstruction in relation to the seed distribution, even without accurate registration with the prostatic volume, can likely identify an inadequate implant intraoperatively and guide corrective seed placement.
METHODS AND MATERIALS
A total of 102 Pd-103 implants performed by standard techniques, using a modified peripheral loading pattern, were studied. A postimplant computed tomography (CT) scan was obtained 2-4 h after the implant. The contoured images and sources were entered into a Varian Variseed 7.0 treatment planning system. Dosimetric parameters analyzed included the percent of the postimplant prostate or rectal volume covered by the prescription dose (V100), and the dose that covers 90% of the postimplant prostate volume (D90). Isodose patterns were analyzed at midprostate, and for the entire prostate. Adverse isodose patterns were defined as gaps, holes, islands. Isodose gaps are subprescription intervals between the prostatic margin and the prescription isodose. Isodose holes are regions of subprescription dose within the prostate. Isodose islands are isolated regions > or =prescription dose inside the prostatic margins.
RESULTS
Characteristic isodose patterns were predictive for V100 values. Midprostatic isodose holes were seen in 55% of patients with a V100 < 80%, 5% of patients with a V100 of 80-90%, and only 1% of patients with a V100 > 90%. When analyzing the entire prostate, isodose holes were seen in 55% of patients with a V100 < 80%, 18% of patients with a V100 of 80-90%, and 9% of patients with a V100 > 90%. Midprostatic isodose islands were seen in 55% of patients with a V100 < 80%, 5% of patients with a V100 of 80-90%, and no patient with a V100 > 90%. When analyzing the entire prostate, isodose islands were seen in all patients with V100 < 80%, 36% of patients with a V100 of 80-90%, and only 1% of patients with a V100 > 90%. The likelihood of a V100 less than 80% was best predicted by the presence of isodose holes or islands at midprostate. Patients with either finding had an 86% chance of having a V100 < 80%.
CONCLUSIONS
These semiquantitative findings can provide practical guidelines for intraoperative dosimetry, to provide a more rational guide to intraoperative postimplant assessment and modification. If isodose holes or islands are seen within the implanted volume, additional seeds are added to the affected region to obtain a V100 > 80%. | 10.1016/s0360-3016(03)00527-3 |
pubmed_796_647 | Insulin and insulin-like growth factor (IGF)-I inhibit intracellular protein degradation in a variety of different cell types. In the present studies, the IGF-I-induced inhibition of protein metabolism in Chinese hamster ovary (CHO) cells was found to be blocked by polyclonal antibodies to the IGF-II/mannose-6-phosphate phosphate (Man-6-P) receptor, but not by control immunoglobulin. In contrast, these antibodies had no effect on the ability of IGF-I to stimulate glucose uptake in the same cells. The antibodies to the IGF-II/Man-6-P receptor also inhibited the effect of IGF-I and insulin on protein catabolism in human foreskin fibroblasts and human hepatoma cells, respectively. Moreover, CHO cells overexpressing a cDNA coding for the IGF-II/Man-6-P receptor were found to exhibit an increased effect of insulin on protein catabolism. In contrast, the insulin stimulation of glucose uptake is the same in these transfected cells as in the parental CHO cells. These results implicate the IGF-II/Man-6-P receptor in the insulin- and IGF-I-induced inhibition of protein catabolism. | 10.1210/mend-3-6-901 |
pubmed_741_14165 | Larsen syndrome is characterised by congenital anterior dislocation of the knees, associated with other joint dislocations, and a characteristic facies. Autosomal recessive and dominant inheritance have been proposed. A brother and a sister with consanguineous parents, suggesting autosomal recessive inheritance, were found to have the typical features of Larsen syndrome. In addition, they had severe cardiac manifestations, never reported before in familial cases of the syndrome. We suggest that the recessive form is probably more severe than the dominant form because of the frequent presence of concomitant cardiac anomalies. | 10.1136/jmg.20.6.422 |
pubmed_677_6211 | Most site-specific recombinases can be grouped into two mechanistically distinct families. Whereas tyrosine recombinases exchange DNA strands through a Holliday intermediate, serine recombinases such as Hin generate double-strand breaks in each recombining partner. Here, site-directed protein crosslinking is used to elucidate the configuration of protein subunits and DNA within the Hin synaptic complex and to follow the movement of protein subunits during DNA strand exchange. Our results show that the protein interface mediating synapsis is localized to a region within the catalytic domains, thereby positioning the DNA strands on the outside of the Hin tetrameric complex. Unexpected crosslinks between residues within the dimerization helices provide evidence for a conformational change that accompanies DNA cleavage. We demonstrate that the Hin subunits, which are linked to the cleaved DNA ends by serine-phosphodiester bonds, translocate between synapsed dimers to exchange the DNA strands. | 10.1016/j.cell.2004.09.010 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.